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<p>Dear Andrew, </p>
<p><br>
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<p>thank you for your quick answer and sorry for the incorrect link. Here is the correct one:<br>
</p>
<p><a href="http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Ticket?tl=V52sRNBloG5lhKfU">http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Ticket?tl=V52sRNBloG5lhKfU</a></p>
<p><br>
</p>
<p>However, I do really see no reason to exclude variants from co-located annotations because of variant QC and why this is the default behaviour. I understand VEP as an annotation tool which should add information of other databases. Of course it's a valuable
information to know that a variant is flagged as bad quality by some resource but this should not result in completely ignoring the information that other databases have collected for this variant.</p>
<p>I would strongly recommend to set the failed option by default to 0, because especially in my case it can lead to a resource-intensive research on supposedly rare variants, because one has not checked manually, whether there is already information available
that was expected to be annotated by VEP.</p>
<p>Of course, everyone should read the whole documentation of a tool but on the other hand software should be developed that default options result in (rather) expected than unexpected behaviour.<br>
</p>
<p><br>
</p>
<p>Kind regards,</p>
<p>Tim<br>
</p>
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<div id="divRplyFwdMsg" dir="ltr"><font style="font-size:11pt" face="Calibri, sans-serif" color="#000000"><b>Von:</b> Dev <dev-bounces@ensembl.org> im Auftrag von Andrew Parton <aparton@ebi.ac.uk><br>
<b>Gesendet:</b> Freitag, 17. April 2020 20:08<br>
<b>An:</b> Ensembl developers list<br>
<b>Betreff:</b> Re: [ensembl-dev] Missing AF annotation</font>
<div> </div>
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<div>Hi,
<div class=""><br class="">
</div>
<div class="">I’ve had a quick look at this variant, and there are a couple of factors at play here:</div>
<div class=""><br class="">
</div>
<div class="">
<ol class="MailOutline">
<li class="">On GRCh37 then the variant has been flagged as failed - <a href="http://grch37.ensembl.org/Homo_sapiens/Variation/Explore?v=rs10614;vdb=variation" class="">http://grch37.ensembl.org/Homo_sapiens/Variation/Explore?v=rs10614;vdb=variation</a> - however
this status is changing for Ensembl 100, which is scheduled for release at the end of April, so the frequencies should appear then. If you’re interested, you can read more about failed variants here: <a href="https://www.ensembl.org/info/genome/variation/prediction/variant_quality.html" class="">https://www.ensembl.org/info/genome/variation/prediction/variant_quality.html</a></li><li class="">The VEP ticket you’ve attached is using GRCh38 - you can find web VEP for GRCh37 at <a href="http://grch37.ensembl.org/Tools/VEP" class="">http://grch37.ensembl.org/Tools/VEP</a></li><li class="">You can include failed variants in your annotations with both web VEP and command line VEP. On the web, clicking the ‘include flagged variants’ checkbox will include these variants in your annotations (see <a href="http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?tl=XKZlzw60sPRnr8HF-6129418" class="">http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?tl=XKZlzw60sPRnr8HF-6129418</a>),
and you can use the option ‘—failed 1’ to include these within your command line output.</li></ol>
<div class=""><br class="">
</div>
<div class="">Kind Regards,</div>
<div class="">Andrew</div>
<div><br class="">
<blockquote type="cite" class="">
<div class="">On 17 Apr 2020, at 15:38, Jeske, Tim <<a href="mailto:Tim.Jeske@med.uni-muenchen.de" class="">Tim.Jeske@med.uni-muenchen.de</a>> wrote:</div>
<br class="Apple-interchange-newline">
<div class=""><span dir="ltr" class="" style="font-family:Calibri,Arial,Helvetica,sans-serif; font-size:12pt; font-style:normal; font-weight:normal; letter-spacing:normal; text-align:start; text-indent:0px; text-transform:none; white-space:normal; word-spacing:0px; background-color:white; text-decoration:none">
<div class="" style="margin-top:0px; margin-bottom:0px">Dear VEP developers,<span class="Apple-converted-space"> </span></div>
<div class=""><font class="" face="Calibri,Arial,Helvetica,sans-serif">
<div class="">
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">I found a frequent variant for which VEP does not correctly report allele frequencies (neither 1000G, nor ESP, nor gnomAD). I've tested both online and command line VEP for GRCh37.</div>
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">The variant is located on chromosome 7, position 74193668 and changes the G to an A.<span class="Apple-converted-space"> </span><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">Here is the link to gnomAD:<span class="Apple-converted-space"> </span><a href="https://gnomad.broadinstitute.org/variant/7-74193668-G-A?dataset=gnomad_r2_1" target="_blank" class="">https://gnomad.broadinstitute.org/variant/7-74193668-G-A?dataset=gnomad_r2_1</a></div>
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
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<div class="" style="margin-top:0px; margin-bottom:0px">And here is the annotation of VEP:</div>
<div class="" style="margin-top:0px; margin-bottom:0px"><a href="https://www.ensembl.org/Multi/Tools/VEP/Ticket?tl=dIJTZhzghOPHidSp" target="_blank" class="">https://www.ensembl.org/Multi/Tools/VEP/Ticket?tl=dIJTZhzghOPHidSp</a><br class="">
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<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
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<div class="" style="margin-top:0px; margin-bottom:0px">VEP does not report any AF for the variant and thus it's easily considered as a very rare variants although it's highly frequent.</div>
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">Is there possibly an obvious explanation for this behavior that I have overlooked? Or is it actually a bug?</div>
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">I'm looking very much forward to your reply!</div>
<div class="" style="margin-top:0px; margin-bottom:0px"><br class="">
</div>
<div class="" style="margin-top:0px; margin-bottom:0px">Best regards</div>
<div class="" style="margin-top:0px; margin-bottom:0px">Tim Jeske</div>
</div>
</font></div>
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