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<p>Hi Wallace,</p>
<p>RefSeq transcripts occasionally differ from the genome assembly
sequence. We calculate HGVS based on the reference assembly, so in
a small number of cases, discrepancies can arise</p>
<p>This is particularly an issue for GRCh37 as many rare reference
alleles have been replaced in the creation of GRCh38. If you look
at the results for rs9332964/ NC_000002.12:g.31529325C>T on
GRCh38, you will see the predicted HGVS is
NM_000348.3:c.680G>A, as you would expect.</p>
<p>We have recently started taking alignments NCBI provide into
account when calling consequences on RefSeq sequences, and plan to
update VEP to use these alignments in HGVS creation, though this
will not be a quick process.</p>
<p>Best wishes,</p>
<p>Sarah<br>
</p>
<br>
<div class="moz-cite-prefix">On 01/02/2018 03:59, Wallace Ko wrote:<br>
</div>
<blockquote type="cite"
cite="mid:CAMsJki0GtLLUjFcdx86vWP0ipH_FQAk2-KhpKBSqD7KQ2MKkVA@mail.gmail.com">
<div dir="ltr">Hello,
<div><br>
</div>
<div>For the variant NC_000002.11:g.<wbr>31754395C>T, VEP
GRCh37 gives HGVSc of <a
href="http://grch37.rest.ensembl.org/vep/human/hgvs/NC_000002.11:g.31754395C%3ET?content-type=application/json&refseq=1&hgvs=1"
target="_blank" moz-do-not-send="true">NM_000348.3:c.679G>A</a> (<wbr>rs9332964).</div>
<div><br>
</div>
<div>By searching dbSNP, we can see that GRCh38 HGVS of <span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline">rs9332964
is NC_000002.12:g.31529325C>T and VEP GRCh38 gives HGVSc
of <a
href="http://rest.ensembl.org/vep/human/hgvs/NC_000002.12:g.31529325C%3ET?content-type=application/json&refseq=1&hgvs=1"
target="_blank" moz-do-not-send="true">NM_000348.3:c.680G>A</a>.</span></div>
<div><br>
</div>
<div>Searching ClinVar, NM_000348.3:c.680G>A gives result
that correspond to <span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline">NC_000002.11:g.</span><wbr
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial"><span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline">31754395C>T
while NM_000348.3:c.679G>A doesn't.</span></div>
<div><span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline"><br>
</span></div>
<div><span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline">Querying <span
style="color:rgb(34,34,34);font-family:arial,sans-serif;font-size:small;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;font-weight:400;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px;background-color:rgb(255,255,255);text-decoration-style:initial;text-decoration-color:initial;float:none;display:inline">NM_000348.3:c.679G>A
in</span> <a
href="https://mutalyzer.nl/name-checker?description=NM_000348.3%3Ac.679G%3EA"
moz-do-not-send="true">Mutalyzer Name Checker</a>, an
error is shown that the reference base should be C instead
of G. This make me wonder if the HGVSc from VEP GRCH37 is
incorrect.</span></div>
<div><br clear="all">
<div>
<div class="gmail-m_-682369354622616030gmail_signature">
<div dir="ltr">
<div>
<div dir="ltr">
<div>
<div dir="ltr"><span>Regards,<br>
Wallace Ko</span></div>
</div>
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