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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>
</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">
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charset=windows-1252">
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<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>
<span id="OLK_SRC_BODY_SECTION" style="color: rgb(0, 0, 0);
font-family: Calibri, sans-serif; font-size: 14px;">
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BORDER-RIGHT: medium none; PADDING-TOP: 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>
</div>
<div><br>
</div>
<span id="OLK_SRC_BODY_SECTION">
<div style="font-family:Calibri; font-size:12pt;
text-align:left; color:black; BORDER-BOTTOM: medium
none; BORDER-LEFT: medium none; PADDING-BOTTOM: 0in;
PADDING-LEFT: 0in; PADDING-RIGHT: 0in; BORDER-TOP:
#b5c4df 1pt solid; BORDER-RIGHT: medium none;
PADDING-TOP: 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 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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normal; letter-spacing: normal; orphans:
auto; text-align: start; text-indent: 0px;
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widows: auto; word-spacing: 0px;
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Calibri, sans-serif; font-size: 14px;"
class="">
Hello -</div>
<div style="font-style: normal;
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normal; letter-spacing: normal; orphans:
auto; text-align: start; text-indent: 0px;
text-transform: none; white-space: normal;
widows: auto; word-spacing: 0px;
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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="">
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;
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;
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class="">
For example:</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;
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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: Helvetica; font-size:
12px; font-style: normal; font-variant-caps:
normal; font-weight: normal; letter-spacing:
normal; orphans: auto; text-align: start;
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white-space: normal; widows: auto;
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<font class="" face="Calibri,sans-serif"><br
class="">
</font></div>
<div style="font-style: normal;
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normal; letter-spacing: normal; orphans:
auto; text-align: start; text-indent: 0px;
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widows: auto; word-spacing: 0px;
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class="">
Thanks so much,</div>
<div style="font-style: normal;
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class="">
<br class="">
</div>
<div style="font-style: normal;
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normal; letter-spacing: normal; orphans:
auto; text-align: start; text-indent: 0px;
text-transform: none; white-space: normal;
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class="">
Ann </div>
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