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<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>
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<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>
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<div>Thanks so much,</div>
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<div>Ann</div>
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<span style="font-weight:bold">From: </span>Ann Black-Ziegelbein <<a 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 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>
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<div>Thanks Sarah -</div>
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<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>
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<div>When do you foresee the GRCh37 update taking place? </div>
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<div>Thanks again for all your help,</div>
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<div>Ann</div>
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<span style="font-weight:bold">From: </span><<a href="mailto:dev-bounces@ensembl.org">dev-bounces@ensembl.org</a>> on behalf of Sarah Hunt <<a href="mailto:seh@ebi.ac.uk">seh@ebi.ac.uk</a>><br>
<span style="font-weight:bold">Reply-To: </span>Ensembl developers list <<a 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 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>
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<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>
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<br>
<div class="moz-cite-prefix">On 01/02/2017 19:02, Black-Ziegelbein, Elizabeth A wrote:<br>
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<blockquote cite="mid:20170201190248.98AE6230028_89230D8B@hx-mx1.ebi.ac.uk" type="cite">
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<div style="color: rgb(0, 0, 0); font-family: Calibri,
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Good afternoon -</div>
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<div style="color: rgb(0, 0, 0); font-family: Calibri,
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I recently ran across a variant annotation from VEP that did not provide any SIFT annotation.</div>
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sans-serif; font-size: 14px;">
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<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>
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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>
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<div><font face="Menlo" size="2">Ann</font></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 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>
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<div>Thanks so much :)</div>
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<div>Ann</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 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>
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Dear Ann,
<div class=""><br class="">
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<div class="">you can find version information in the following file of your cache file directory:</div>
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<div class="">~/.vep/homo_sapiens_merged/84_GRCh37/info.txt</div>
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<div class="">Assuming you use ~/.vep to store your cache files.</div>
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<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>
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<div class="">HTH,</div>
<div class="">Anja</div>
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<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>
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Hello -</div>
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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>
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For example:</div>
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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>
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Thanks so much,</div>
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Ann </div>
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