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<p>Hi Ann,</p>
<p>Thanks for the additional information. We are looking into why
some protein sequences have no data and can tell you more about
timelines when we understand the issue. As you are using the VEP
script, we would be able to supply updated data files outside our
release cycle. If you send the list we can use it to check the
updated data.<br>
</p>
Best wishes,<br>
<br>
Sarah<br>
<br>
<div class="moz-cite-prefix">On 02/02/2017 16:28, Black-Ziegelbein,
Elizabeth A wrote:<br>
</div>
<blockquote
cite="mid:20170202162918.90B6323004C_8935E5EB@hx-mx1.ebi.ac.uk"
type="cite">
<meta http-equiv="Content-Type" content="text/html;
charset=windows-1252">
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<div>
<div>Just a quick update. In a quick query across our
variants in about 120 genes, there are over 12,000
HIGH/MODERATE SNPs which have a missing SIFT score (which is
present in dbNSFP). This does not include cases where there
are multiple transcripts, and the SIFT score is present on a
subset of those transcripts (but present for all transcripts
in dbNSFP).</div>
<div><br>
</div>
<div>We really appreciate your help & advice. It would
really helpful to get an update on when this might be fixed
for GRCh37. We are not ready to move onto GRCh38 in our
pipelines yet. </div>
<div><br>
</div>
<div>Thanks so much,</div>
<div><br>
</div>
<div>Ann</div>
<div>
</div>
</div>
</div>
<div><br>
</div>
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<span style="font-weight:bold">From: </span>Ann
Black-Ziegelbein <<a moz-do-not-send="true"
href="mailto:elizabeth-black@uiowa.edu">elizabeth-black@uiowa.edu</a>><br>
<span style="font-weight:bold">Date: </span>Thursday,
February 2, 2017 at 7:18 AM<br>
<span style="font-weight:bold">To: </span>Ensembl developers
list <<a moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Subject: </span>Re:
[ensembl-dev] Sift scores from VEP<br>
</div>
<div><br>
</div>
<div>
<div style="word-wrap: break-word; -webkit-nbsp-mode: space;
-webkit-line-break: after-white-space; color: rgb(0, 0, 0);
font-size: 14px; font-family: Calibri, sans-serif;">
<div>
<div>Thanks Sarah -</div>
<div><br>
</div>
<div>I found several other instances as well where there
was only one transcript that was annotated with SIFT
with others having it missing. In these scenarios too,
dbNSFP as well as the SIFT database have the scores for
the VEP missing SIFT score. Let me know if I should
send on a list? I should have a count on how prevalent
this is later today for a targeted set of genes.</div>
<div><br>
</div>
<div>When do you foresee the GRCh37 update taking place? </div>
<div><br>
</div>
<div>Thanks again for all your help,</div>
<div><br>
</div>
<div>Ann</div>
<div>
</div>
</div>
<div><br>
</div>
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<span style="font-weight:bold">From: </span><<a
moz-do-not-send="true"
href="mailto:dev-bounces@ensembl.org">dev-bounces@ensembl.org</a>>
on behalf of Sarah Hunt <<a moz-do-not-send="true"
href="mailto:seh@ebi.ac.uk">seh@ebi.ac.uk</a>><br>
<span style="font-weight:bold">Reply-To: </span>Ensembl
developers list <<a moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Date: </span>Thursday,
February 2, 2017 at 5:16 AM<br>
<span style="font-weight:bold">To: </span>Ensembl
developers list <<a moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Subject: </span>Re:
[ensembl-dev] Sift scores from VEP<br>
</div>
<div><br>
</div>
<div>
<div bgcolor="#FFFFFF" text="#000000">
<p><br>
</p>
<p>Hi Ann,</p>
<p>Thanks for reporting this. Checking at this variant
in GRCh38, SIFT scores are available for the protein
coding transcripts which suggests the lack of scores
for GRCh37 may be due to a technical issue. We will
look into this when we next update our GRCh37
database. <br>
</p>
<p>Best wishes,</p>
<p>Sarah<br>
</p>
<br>
<div class="moz-cite-prefix">On 01/02/2017 19:02,
Black-Ziegelbein, Elizabeth A wrote:<br>
</div>
<blockquote
cite="mid:20170201190248.98AE6230028_89230D8B@hx-mx1.ebi.ac.uk"
type="cite">
<div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
Good afternoon -</div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
<br>
</div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
I recently ran across a variant annotation from
VEP that did not provide any SIFT annotation.</div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
<br>
</div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
1: <span style="font-family: Menlo; font-size:
11px;">103343580 C > A (GRCh 37
coordinates)</span></div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
<span style="font-family: Menlo; font-size:
11px;"><br>
</span></div>
<div><font face="Calibri,sans-serif">In dbNSFP,
and by directly querying the most recent
download of the SIFT scores from SIFT (</font><a
moz-do-not-send="true"
href="http://sift.bii.a-star.edu.sg/sift4g/public/Homo_sapiens/GRCh37.74.zip"
style="color: rgb(0, 0, 0); font-family:
Menlo; font-size: 11px;">http://sift.bii.a-star.edu.sg/sift4g/public/Homo_sapiens/GRCh37.74.zip</a><font
face="Menlo" size="2">) show this SNP as
having a SIFT score of 0 – damaging. It is a
missense variant. I found the documentation
about how SIFT and Polyphen scores are
computed by VEP – but just wanted to
check/verify that this should be expected and
not some type of error? I have found more than
one instance of this.</font></div>
<div><font face="Menlo" size="2"><br>
</font></div>
<div><font face="Menlo" size="2">Thanks for your
thoughts -</font></div>
<div><font face="Menlo" size="2"><br>
</font></div>
<div><font face="Menlo" size="2">Ann</font></div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
<span style="font-family: Menlo; font-size:
11px;"><br>
</span></div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
</div>
</div>
<div style="color: rgb(0, 0, 0); font-family:
Calibri, sans-serif; font-size: 14px;">
<br>
</div>
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0, 0); font-family: Calibri, sans-serif;
font-size: 14px;">
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3pt">
<span style="font-weight:bold">From: </span><<a
moz-do-not-send="true"
href="mailto:dev-bounces@ensembl.org">dev-bounces@ensembl.org</a>>
on behalf of Ann Black-Ziegelbein <<a
moz-do-not-send="true"
href="mailto:elizabeth-black@uiowa.edu">elizabeth-black@uiowa.edu</a>><br>
<span style="font-weight:bold">Reply-To: </span>Ensembl
developers list <<a moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Date: </span>Tuesday,
October 11, 2016 at 11:43 AM<br>
<span style="font-weight:bold">To: </span>Ensembl
developers list <<a moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Subject: </span>Re:
[ensembl-dev] Sift/Polyphen scores from VEP
cache vs. dbNSFP<br>
</div>
<div><br>
</div>
<div>
<div style="word-wrap: break-word;
-webkit-nbsp-mode: space; -webkit-line-break:
after-white-space; color: rgb(0, 0, 0);
font-size: 14px; font-family: Calibri,
sans-serif;">
<div>
<div>
<div>Thanks so much :)</div>
<div><br>
</div>
<div>Ann</div>
</div>
</div>
<div><br>
</div>
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<span style="font-weight:bold">From: </span><<a
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href="mailto:dev-bounces@ensembl.org">dev-bounces@ensembl.org</a>>
on behalf of Anja Thormann <<a
moz-do-not-send="true"
href="mailto:anja@ebi.ac.uk">anja@ebi.ac.uk</a>><br>
<span style="font-weight:bold">Reply-To: </span>Ensembl
developers list <<a
moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Date: </span>Tuesday,
October 11, 2016 at 11:35 AM<br>
<span style="font-weight:bold">To: </span>Ensembl
developers list <<a
moz-do-not-send="true"
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
<span style="font-weight:bold">Subject: </span>Re:
[ensembl-dev] Sift/Polyphen scores from
VEP cache vs. dbNSFP<br>
</div>
<div><br>
</div>
<div>
<div style="word-wrap: break-word;
-webkit-nbsp-mode: space;
-webkit-line-break: after-white-space;"
class="">
Dear Ann,
<div class=""><br class="">
</div>
<div class="">you can find version
information in the following file of
your cache file directory:</div>
<div class=""><br class="">
</div>
<div class="">~/.vep/homo_sapiens_merged/84_GRCh37/info.txt</div>
<div class=""><br class="">
</div>
<div class="">Assuming you use ~/.vep to
store your cache files.</div>
<div class=""><br class="">
</div>
<div class="">source_polyphen<span class="Apple-tab-span" style="white-space:pre"></span>2.2.2</div>
<div class="">source_sift<span class="Apple-tab-span" style="white-space:pre"> </span>
sift5.2.2</div>
<div class=""><br class="">
</div>
<div class="">We provide more
information on how we run SIFT and
PolyPhen here:</div>
<div class=""><a moz-do-not-send="true"
href="http://www.ensembl.org/info/genome/variation/predicted_data.html#sift"
class="">http://www.ensembl.org/info/genome/variation/predicted_data.html#sift</a></div>
<div class=""><br class="">
</div>
<div class="">HTH,</div>
<div class="">Anja</div>
<div class=""><br class="">
</div>
<div class=""><br class="">
</div>
<div class="">
<div>
<blockquote type="cite" class="">
<div class="">On 11 Oct 2016, at
17:24, Black-Ziegelbein,
Elizabeth A <<a
moz-do-not-send="true"
href="mailto:elizabeth-black@uiowa.edu"
class="">elizabeth-black@uiowa.edu</a>>
wrote:</div>
<br
class="Apple-interchange-newline">
<div class="">
<div style="font-style: normal;
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class="">
Hello -</div>
<div style="font-style: normal;
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start; text-indent: 0px;
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auto; word-spacing: 0px;
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class="">
<br class="">
</div>
<div style="font-style: normal;
font-variant-caps: normal;
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letter-spacing: normal;
orphans: auto; text-align:
start; text-indent: 0px;
text-transform: none;
white-space: normal; widows:
auto; word-spacing: 0px;
-webkit-text-stroke-width:
0px; font-family: Calibri,
sans-serif; font-size: 14px;"
class="">
We are running a local
installation of VEP (v84) and
are running it with –offline
and –cache parameters. Caches
were installed with the VEP
script (we did not use custom
caches - using <span
style="font-family: Menlo;
font-size: 11px;" class="">homo_sapiens_merged/84_GRCh37</span>).
I have noticed in some cases
the SIFT and Polyphen scores
for transcripts are different
than what is reported in
dbNSFP3 for a variant. I was
wondering what version of SIFT
and Polyphen scores are
included in the pre–built
caches or if there are
thoughts on why they would be
different. Additionally is it
the polyphen v2 score or
polyphen?</div>
<div style="font-style: normal;
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class="">
<br class="">
</div>
<div style="font-style: normal;
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font-weight: normal;
letter-spacing: normal;
orphans: auto; text-align:
start; text-indent: 0px;
text-transform: none;
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auto; word-spacing: 0px;
-webkit-text-stroke-width:
0px; font-family: Calibri,
sans-serif; font-size: 14px;"
class="">
For example:</div>
<div style="font-style: normal;
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letter-spacing: normal;
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start; text-indent: 0px;
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auto; word-spacing: 0px;
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sans-serif; font-size: 14px;"
class="">
<br class="">
</div>
<div style="font-style: normal;
font-variant-caps: normal;
font-weight: normal;
letter-spacing: normal;
orphans: auto; text-align:
start; text-indent: 0px;
text-transform: none;
white-space: normal; widows:
auto; word-spacing: 0px;
-webkit-text-stroke-width:
0px; font-family: Calibri,
sans-serif; font-size: 14px;"
class="">
Missense variant
6:33143391:G>A has no SIFT
scores available for any
transcript from the VEP
annotation. <font class=""
face="Calibri,sans-serif">From
dbNSFP 3.1, the same variant
has the following SIFT
scores: 0.285;0.29;0.307
for the following
transcripts: </font><font
class=""
face="Calibri,sans-serif">ENST00000374708;ENST00000341947;ENST00000361917.</font></div>
<div style="font-family:
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start; text-indent: 0px;
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0px;" class="">
<font class=""
face="Calibri,sans-serif"><br
class="">
</font></div>
<div style="font-style: normal;
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auto; word-spacing: 0px;
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0px; font-family: Calibri,
sans-serif; font-size: 14px;"
class="">
Thanks so much,</div>
<div style="font-style: normal;
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class="">
<br class="">
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class="">
Ann </div>
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<pre wrap="">_______________________________________________
Dev mailing list <a moz-do-not-send="true" class="moz-txt-link-abbreviated" href="mailto:Dev@ensembl.org">Dev@ensembl.org</a>
Posting guidelines and subscribe/unsubscribe info: <a moz-do-not-send="true" class="moz-txt-link-freetext" href="http://lists.ensembl.org/mailman/listinfo/dev">http://lists.ensembl.org/mailman/listinfo/dev</a>
Ensembl Blog: <a moz-do-not-send="true" class="moz-txt-link-freetext" href="http://www.ensembl.info/">http://www.ensembl.info/</a></pre>
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<pre wrap="">_______________________________________________
Dev mailing list <a class="moz-txt-link-abbreviated" href="mailto:Dev@ensembl.org">Dev@ensembl.org</a>
Posting guidelines and subscribe/unsubscribe info: <a class="moz-txt-link-freetext" href="http://lists.ensembl.org/mailman/listinfo/dev">http://lists.ensembl.org/mailman/listinfo/dev</a>
Ensembl Blog: <a class="moz-txt-link-freetext" href="http://www.ensembl.info/">http://www.ensembl.info/</a>
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