<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 Wallace,<div class=""><br class=""></div><div class="">Thank you for your query, I’ve had a look and it seems like there is an issue mapping these transcripts to the reference genome.</div><div class=""><br class=""></div><div class="">To provide RefSeq annotations within VEP, we use NCBI-provided GFF files (to provide the transcript set) and BAM files (to align these transcripts to the reference genome). The FAILED value in BAM_EDIT shows that VEP is failing to map the transcript to the reference genome using this BAM file, so as a best guess VEP uses the reference genome as a transcript sequence in this location. Meaning that, depending on how much the RefSeq transcript differs from the reference genome, it is possible that the HGVS will be incorrect.</div><div class=""><br class=""></div><div class="">For the second result, there’s no mapping within the BAM file for this transcript, so we can’t map it to the reference genome.</div><div class=""><br class=""></div><div class="">Filtering transcripts like this is a little tricky - you could remove all transcripts with BAM_EDIT=FAILED attached, however identifying transcripts where an alignment is simply missing from the NCBI-provided BAM won’t be covered in this case. We do have flags to identify these transcripts within our GRCh38 dataset, however we do not have a recommended practise to remove these within GRCh37 I’m afraid. Additionally, we know that there are fewer transcripts that land in both of these cases within our GRCh38 dataset, however that doesn’t help your current position. </div><div class=""><br class=""></div><div class="">Sorry that I couldn’t give you a more helpful response. If you have any further questions, please don’t hesitate to ask.</div><div class=""><br class=""></div><div class="">Kind Regards,</div><div class="">Andrew</div><div><br class=""><blockquote type="cite" class=""><div class="">On 18 Feb 2019, at 14:57, Wallace Ko <<a href="mailto:myko@l3-bioinfo.com" class="">myko@l3-bioinfo.com</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class="">Hi,<div class=""><br class=""></div><div class="">When the variant '11 70742675 G/A' is annotated with VEP, there are 2 results with high and moderate impact:</div><div class=""><ol class=""><li class="">NM_012309.4:c.958C>T (cDNA position: 1070)<br class=""></li><li class="">NM_012309.3:c.959C>T (cDNA position: 1037)<br class=""></li></ol><div class="">For the first result, the actual nucleotide at NM_012309.4:n.1070 is T. May I assume that the FAILED value in BAM EDIT field indicates that the HGVS is incorrect?</div></div><div class=""><br class=""></div><div class="">For the second result, the actual nucleotide at NM_012309.3:n.1037 is A. And the result of blat on NC_000011.9 show that NM_012309.3:n.1037 aligns to nowhere. I wonder how VEP would produce result. And do you have any suggested practice to filter them?</div><div class=""><br class=""></div><div class="">Thanks,</div><div class=""><div class=""><div dir="ltr" class="gmail_signature"><div dir="ltr" class=""><div class="">Wallace Ko</div></div></div></div></div></div></div></div></div></div></div>
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