<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=""><p style="background-color: rgb(255, 255, 255);" class="">Dear Beat,</p><div class="">First of all thank you for reporting the problem about the strange allele frequencies. This has been corrected. Please check again the REST output: <a href="http://rest.ensembl.org/vep/hsapiens/id/rs351771?ExAC=1&content-type=application/json" class="">http://rest.ensembl.org/vep/hsapiens/id/rs351771?ExAC=1&content-type=application/json</a></div><div class=""><br class=""></div><div class="">Secondly, we recently replaced the usage of _<i class="">maf </i>with _<i class="">af </i>because of the exact reasons for confusion which you mention. We are also no longer reporting the minor allele and and minor allele frequency with the VEP.</div><div class=""><br class=""></div><div class=""><span style="background-color: rgb(255, 255, 255);" class="">Unfortunately, we overlooked the usage of </span><i style="background-color: rgb(255, 255, 255);" class="">maf </i><span style="background-color: rgb(255, 255, 255);" class="">in our REST output.</span></div><div class=""><span style="background-color: rgb(255, 255, 255);" class=""><br class=""></span></div><div class=""><span style="background-color: rgb(255, 255, 255);" class="">We will update the REST output to match the output format of the VEP script output. This is planned for release/94.</span></div><div class=""><span style="background-color: rgb(255, 255, 255);" class=""><br class=""></span></div><div class=""><span style="background-color: rgb(255, 255, 255);" class="">To summarise: </span>When annotating a variant with the VEP, the VEP reports allele frequencies from co-located variants. Frequencies are only reported for the non-reference input allele. </div><div class=""><br class=""></div><div class="">The new keys in the REST output will be:</div><div class=""><br class=""></div><div class=""><b class="">AF</b> (global allele frequency (AF) from 1000 Genomes Phase 3)</div><div class=""><b class="">MAX_AF, MAX_AF_POPS</b> (Report the highest allele frequency observed in any population from 1000 genomes, ESP or gnomAD.)</div><div class=""><b class="">AFR_AF, AMR_AF, EAS_AF, EUR_AF, SAS_AF</b> (allele frequency from continental populations (AFR,AMR,EAS,EUR,SAS) of 1000 Genomes Phase 3)</div><div class=""><b class="">AA_AF, EA_AF</b> (allele frequency from NHLBI-ESP)</div><div class=""><b class="">gnomAD_AF, gnomAD_AFR_AF, gnomAD_AMR_AF, gnomAD_ASJ_AF, gnomAD_EAS_AF, gnomAD_FIN_AF, gnomAD_NFE_AF, gnomAD_OTH_AF, gnomAD_SAS_AF</b> (allele frequency from Genome Aggregation Database (gnomAD))</div><div class=""><br class=""></div><div class="">Here is a more detailed description of frequency related output fields: <a href="https://www.ensembl.org/info/docs/tools/vep/script/vep_options.html#existing" class="">https://www.ensembl.org/info/docs/tools/vep/script/vep_options.html#existing</a></div><div class=""><br class=""></div><div class="">For now please don’t be confused by the usage of maf in our REST output.</div><div class=""><br class=""></div><div class=""><b class="">minor_allele_freq and minor_allele</b>: refer<span style="background-color: rgb(255, 255, 255);" class=""> to the frequency of the second most common allele at the position where a sequence variant (such as a SNP) has been identified. In Ensembl, the global MAF is calculated using the allele frequencies across all 1000 Genomes Phase 3 populations.</span></div><div class=""><br class=""></div><div class=""><b class=""><i class="">population</i>_maf and <i class="">population</i>_allele</b> match the input non-reference allele and report the allele frequency as reported for the respective <i class="">population</i></div><div class=""><i class=""><br class=""></i></div><div class=""><i class=""><br class=""></i></div><div class="">Please let me know if you have any further questions,</div><div class=""><br class=""></div><div class="">Kind regards,</div><div class="">Anja</div><div><br class=""><blockquote type="cite" class=""><div class="">On 10 Apr 2018, at 12:35, Wolf Beat <<a href="mailto:Beat.Wolf@hefr.ch" class="">Beat.Wolf@hefr.ch</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div class="">Hi, i have a question out the minor_allele field of the colocated_variants field in the VEP response.<br class=""><br class=""><br class="">for rs351771 (G>A) i don't fully understand the logic of the answer:<br class=""><br class=""><br class=""><a href="http://rest.ensembl.org/vep/hsapiens/id/rs351771?ExAC=1&content-type=application/json" class="">http://rest.ensembl.org/vep/hsapiens/id/rs351771?ExAC=1&content-type=application/json</a><br class=""><br class=""><br class="">What i have trouble understanding is the minor_allele for 1000 genomes (thats minor_allele i think) and for the others.<br class=""><br class="">For all, except minor_alelle, the minor allele is "A". But for minor_allele its "G".<br class=""><br class=""><br class="">From what i can guess, the variant is a little borderline between a variant and a false reference, meaning, the reference sequence might actually be the minor_allele.<br class=""><br class=""><br class="">But what i don't understand are the numbers from gnomad etc. reported by VEP. If i read the http://gnomad.broadinstitute.org/variant/5-112164561-G-A website correctly, the frequency of A should be quite high, 50%+. Yet VEP tells me that the frequency of A in gnomad is way under 1%.<br class=""><br class=""><br class="">Am I missing something here? Can somebody help me to better understand the output of VEP?<br class=""><br class=""><br class="">Kind regards<br class=""><br class=""><br class="">Beat Wolf<br class="">_______________________________________________<br class="">Dev mailing list Dev@ensembl.org<br class="">Posting guidelines and subscribe/unsubscribe info: http://lists.ensembl.org/mailman/listinfo/dev<br class="">Ensembl Blog: http://www.ensembl.info/<br class=""></div></div></blockquote></div><br class=""></body></html>