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    <p><br>
    </p>
    <p>Hi Wallace,</p>
    <p>Both NCBI and Ensembl stopped creating new gene annotations on
      GRCh37 a long time ago - late 2013 and early 2014 respectively.<br>
    </p>
    <p>NCBI released a mapping of the then current set of GRCh38-derived
      RefSeq transcripts to GRCh37 in January 2017. (See:
<a class="moz-txt-link-freetext" href="ftp://ftp.ncbi.nlm.nih.gov/genomes/H_sapiens/GRCh37.p13_interim_annotation/README">ftp://ftp.ncbi.nlm.nih.gov/genomes/H_sapiens/GRCh37.p13_interim_annotation/README</a>
      for details).  We added these to our GRCh37 database in Ensembl
      90, in the summer of 2017, with SIFT and PolyPhen2 results. <br>
    </p>
    <p>We are not expecting any new transcript data for GRCh37, so there
      is nothing new to analyse. If we switch to new versions of SIFT or
      Polyphen2 or find ways to reduce the failure rate, we may update
      the GRCh37 results. We don't currently plan a version change and
      it would be announced if we did this as results would change.</p>
    <p>Best wishes,</p>
    <p>Sarah<br>
    </p>
    <div class="moz-cite-prefix">On 04/01/2019 02:16, Wallace Ko wrote:<br>
    </div>
    <blockquote type="cite"
cite="mid:CA+DTqFd+bDvQY=BDavLwcdc6Q7hmqicpyfu0+gDbuf9Kn_KgYw@mail.gmail.com">
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      <div dir="ltr">Hi Sarah,
        <div><br>
        </div>
        <div>Thanks for your explanation.</div>
        <div>Does it mean that SIFT and PolyPhen2 scores for RefSeq
          transcript for GRCh37 are now also calculated (instead of
          mapping from Ensembl transcript) but at a longer update
          interval?</div>
        <div><br clear="all">
          <div>
            <div dir="ltr" class="gmail_signature"
              data-smartmail="gmail_signature">
              <div dir="ltr">Best,
                <div>Wallace</div>
              </div>
            </div>
          </div>
          <br>
        </div>
      </div>
      <br>
      <div class="gmail_quote">
        <div dir="ltr">On Thu, Jan 3, 2019 at 1:09 AM Sarah Hunt <<a
            href="mailto:seh@ebi.ac.uk" moz-do-not-send="true">seh@ebi.ac.uk</a>>
          wrote:<br>
        </div>
        <blockquote class="gmail_quote" style="margin:0px 0px 0px
          0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
          <div bgcolor="#FFFFFF">
            <p><br>
            </p>
            <p>Hi Wallace,</p>
            <p>Apologies for the partial response. <br>
            </p>
            <p>Prior to release 90, we did not calculate SIFT and
              PolyPhen2 scores for RefSeq transcripts, though they were
              available for those with translations identical to an
              Ensembl transcript. Although the GRCh37 transcript sets
              have been frozen for some time, we update our GRCh37
              variation data roughly annually, and results from the
              analysis of new Ensembl GRCh38 translations would be made
              available then. <br>
            </p>
            <p>The difference in SIFT results - the change from no data
              to a prediction -  will be due to results for a transcript
              matching NM_000540.2 becoming available in release 88.</p>
            <p>We re-ran our PolyPhen pipeline for e!90 when we noticed
              slightly lower missingness rates after a change of
              hardware. We suspected changes in the cluster set up led
              to less high-memory alignment failures, but were not in a
              position to test this.</p>
            <p>We now routinely calculate SIFT and PolyPhen2 scores for
              RefSeq transcripts for our GRCh38 releases, which happen
              roughly quarterly. Due to the scheduling of when RefSeq
              transcript data becomes available in our release process,
              these scores are available in VEP the release after the
              transcripts are available.<br>
            </p>
            <p>Best wishes,</p>
            <p>Sarah<br>
            </p>
            <br>
            <blockquote type="cite">
              <div class="gmail-m_3254829721660434728moz-cite-prefix">On
                28/12/2018 11:12, Wallace Ko wrote:<br>
              </div>
              <blockquote type="cite">
                <div dir="ltr">
                  <div dir="ltr">
                    <div dir="ltr">
                      <div dir="ltr">
                        <div dir="ltr">
                          <div dir="ltr">
                            <div dir="ltr">
                              <div dir="ltr">Hello,
                                <div><br>
                                </div>
                                <div>For the
                                  variant chr19:g.39075695C>T, the
                                  SIFT and PolyPhen score are changed in
                                  recent versions of VEP.</div>
                                <div><br>
                                </div>
                                <div>
                                  <table dir="ltr"
style="table-layout:fixed;font-size:10pt;font-family:arial,sans,sans-serif;width:0px;border-collapse:collapse;border:none"
                                    cellspacing="0" cellpadding="0"
                                    border="1">
                                    <colgroup><col width="42"><col
                                        width="171"><col width="100"><col
                                        width="167"></colgroup><tbody>
                                      <tr style="height:21px">
                                        <td style="border:1px solid
                                          rgb(0,0,0);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">VEP</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(0,0,0)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">HGVSc</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(0,0,0)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">SIFT</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(0,0,0)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">PolyPhen</td>
                                      </tr>
                                      <tr style="height:21px">
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0)
                                          rgb(0,0,0);overflow:hidden;padding:2px
3px;vertical-align:bottom;text-align:right">87</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">NM_000540.2:c.14759C>T</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">-</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">unknown(0)</td>
                                      </tr>
                                      <tr style="height:21px">
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0)
                                          rgb(0,0,0);overflow:hidden;padding:2px
3px;vertical-align:bottom;text-align:right">88</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">NM_000540.2:c.14759C>T</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">deleterious(0)</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">unknown(0)</td>
                                      </tr>
                                      <tr style="height:21px">
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0)
                                          rgb(0,0,0);overflow:hidden;padding:2px
3px;vertical-align:bottom;text-align:right">89</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">NM_000540.2:c.14759C>T</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">deleterious(0)</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">unknown(0)</td>
                                      </tr>
                                      <tr style="height:21px">
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0)
                                          rgb(0,0,0);overflow:hidden;padding:2px
3px;vertical-align:bottom;text-align:right">90</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">NM_000540.2:c.14759C>T</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">deleterious(0)</td>
                                        <td
                                          style="border-width:1px;border-style:solid;border-color:rgb(204,204,204)
                                          rgb(0,0,0) rgb(0,0,0)
                                          rgb(204,204,204);overflow:hidden;padding:2px
                                          3px;vertical-align:bottom">probably_damaging(0.998)</td>
                                      </tr>
                                    </tbody>
                                  </table>
                                </div>
                                <div><br>
                                </div>
                                <div>The above table shows that
                                  for NM_000540.2:c.14759C>T, SIFT is
                                  changed from  '-' to 'deleterious(0)'
                                  since VEP 88 and PolyPhen is changed
                                  from 'unknown(0)' to
                                  'probably_damaging(0.998)'  since VEP
                                  90.</div>
                                <div><br>
                                </div>
                                <div>There is no change in software
                                  version of SIFT (sift5.2.2) and
                                  PolyPhen (2.2.2) in these versions of
                                  VEP, so I wonder what causes to the
                                  change in the prediction scores.</div>
                                <div><br>
                                </div>
                                <div>Thank you.</div>
                                <div><br clear="all">
                                  <div>
                                    <div dir="ltr"
                                      class="gmail-m_3254829721660434728gmail_signature">
                                      <div dir="ltr">Regards,
                                        <div>Wallace Ko</div>
                                      </div>
                                    </div>
                                  </div>
                                </div>
                              </div>
                            </div>
                          </div>
                        </div>
                      </div>
                    </div>
                  </div>
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