<html><head><meta http-equiv="Content-Type" content="text/html; charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; line-break: after-white-space;" class="">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" style="caret-color: rgb(0, 0, 0); font-family: Calibri, Arial, Helvetica, sans-serif; font-size: 12pt; font-style: normal; font-variant-caps: normal; font-weight: normal; letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: white; text-decoration: none;" class=""><div style="margin-top: 0px; margin-bottom: 0px;" class="">Dear VEP developers,<span class="Apple-converted-space"> </span></div><div class=""><font face="Calibri,Arial,Helvetica,sans-serif" class=""><div class=""><div style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">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 style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">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 style="margin-top: 0px; margin-bottom: 0px;" class="">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 style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">And here is the annotation of VEP:</div><div style="margin-top: 0px; margin-bottom: 0px;" class=""><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=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">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 style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">Is there possibly an obvious explanation for this behavior that I have overlooked? Or is it actually a bug?</div><div style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">I'm looking very much forward to your reply!</div><div style="margin-top: 0px; margin-bottom: 0px;" class=""><br class=""></div><div style="margin-top: 0px; margin-bottom: 0px;" class="">Best regards</div><div style="margin-top: 0px; margin-bottom: 0px;" class="">Tim Jeske</div></div></font></div></span><span style="caret-color: rgb(0, 0, 0); font-family: Calibri, Arial, Helvetica, sans-serif; font-size: 16px; font-style: normal; font-variant-caps: normal; font-weight: normal; letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: rgb(255, 255, 255); text-decoration: none; float: none; display: inline !important;" class=""></span><div style="margin-top: 0px; margin-bottom: 0px; caret-color: rgb(0, 0, 0); font-family: Calibri, Arial, Helvetica, sans-serif; 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