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<p>Hi David,</p>
<p>thanks for the feedback! Yes, the question of reporting the
distance of a variant to the nearest exon junction has come up
before.</p>
<p>In your particular case, are you interested in identifying stop
gained and frameshift variants that are/aren't covered by NMD
using the 50 bp rule, or having your own customizable rule?<br>
</p>
<p>If you are interested in identifying stop gained and frameshifts
that escape NMD (50bp rule) then this functionality is available
and refined in <span style="color: rgb(36, 41, 46); font-family:
-apple-system, system-ui, "Segoe UI", Helvetica,
Arial, sans-serif, "Apple Color Emoji", "Segoe UI
Emoji", "Segoe UI Symbol"; font-size: 16px;
font-style: normal; font-variant-ligatures: normal;
font-variant-caps: normal; font-weight: 400; letter-spacing:
normal; orphans: 2; text-align: start; text-indent: 0px;
text-transform: none; white-space: normal; widows: 2;
word-spacing: 0px; -webkit-text-stroke-width: 0px;
background-color: rgb(255, 255, 255); text-decoration-style:
initial; text-decoration-color: initial; display: inline
!important; float: none;">LOFTEE (</span><a class="moz-txt-link-freetext" href="https://github.com/konradjk/loftee">https://github.com/konradjk/loftee</a>);
it annotates such variants with LoF LC END_TRUNC, the plugin is
taking into consideration UTR splicing and GERP scores.<br>
</p>
<p>If there are cases that you are interested in and are not covered
by the existing plugins, I would be interested to know. Also, we
encourage and accept pull requests on the VEP_plugins
(<a class="moz-txt-link-freetext" href="https://github.com/Ensembl/VEP_plugins">https://github.com/Ensembl/VEP_plugins</a>) git repository for
plugins that would be for wider interest. <span style="color:
rgb(102, 102, 102); font-family: "Luxi Sans",
Helvetica, Arial, Geneva, sans-serif; font-size: 12.8px;
font-style: normal; font-variant-ligatures: normal;
font-variant-caps: normal; font-weight: 400; letter-spacing:
normal; orphans: 2; text-align: start; text-indent: 0px;
text-transform: none; white-space: normal; widows: 2;
word-spacing: 0px; -webkit-text-stroke-width: 0px;
background-color: rgb(255, 255, 255); text-decoration-style:
initial; text-decoration-color: initial; display: inline
!important; float: none;"><span></span></span><span
style="color: rgb(102, 102, 102); font-family: "Luxi
Sans", Helvetica, Arial, Geneva, sans-serif; font-size:
12.8px; font-style: normal; font-variant-ligatures: normal;
font-variant-caps: normal; font-weight: 400; letter-spacing:
normal; orphans: 2; text-align: start; text-indent: 0px;
text-transform: none; white-space: normal; widows: 2;
word-spacing: 0px; -webkit-text-stroke-width: 0px;
background-color: rgb(255, 255, 255); text-decoration-style:
initial; text-decoration-color: initial; display: inline
!important; float: none;"></span></p>
<p>Kind regards,</p>
<p>Irina<br>
</p>
<div class="moz-cite-prefix">On 07/03/2019 17:39, David Tamborero
wrote:<br>
</div>
<blockquote type="cite"
cite="mid:CAMk_RaQyps1a2Axp_2PAEBx0eavbfH6qzGMS7bfrf6U2G7VF4w@mail.gmail.com">
<meta http-equiv="content-type" content="text/html; charset=UTF-8">
<div dir="ltr">
<div>Hi Irina, I have been playing with the plugin (thanks for
that again!). <br>
</div>
<div><br>
</div>
<div>What I am actually interested is in the distance of the
variant to the next exon-exon junction, as defined by the CDS
and not by the 'absolute' bps (including UTR), which is what
determines whether the NMD will act (see <a
href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002296"
moz-do-not-send="true">here</a>), which is what i want to
detect. I was not clear enough on that, apologies.</div>
<div><br>
</div>
<div>In any case, what you re retrieving now is actually also
interesting for other evaluations. Maybe you could include
what you have now and also the coding sequence values ? Again,
note that I address these calculations by my own ad hoc
scripts, so consider to implement it (together with the
location of the frameshift-induced stop codon mentioned
before) just if you believe that it can be of interest for the
community (which i think it does!) <br>
</div>
<div><br>
</div>
<div>br</div>
<div>d<br>
</div>
</div>
<br>
<div class="gmail_quote">
<div dir="ltr" class="gmail_attr">El lun., 4 mar. 2019 a las
18:33, David Tamborero (<<a
href="mailto:david.tamborero@gmail.com"
moz-do-not-send="true">david.tamborero@gmail.com</a>>)
escribió:<br>
</div>
<blockquote class="gmail_quote" style="margin:0px 0px 0px
0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div dir="ltr">
<div>thta s great, i m currently travelling but i will try
it as soon as i back to the lab (and feedback you guys as
appropriate)<br>
</div>
<div><br>
</div>
<div>thanks again!</div>
<div>d<br>
</div>
</div>
<br>
<div class="gmail_quote">
<div dir="ltr" class="gmail_attr">El vie., 1 mar. 2019 a las
16:27, Irina Armean (<<a
href="mailto:iarmean@ebi.ac.uk" target="_blank"
moz-do-not-send="true">iarmean@ebi.ac.uk</a>>)
escribió:<br>
</div>
<blockquote class="gmail_quote" style="margin:0px 0px 0px
0.8ex;border-left:1px solid
rgb(204,204,204);padding-left:1ex">
<div bgcolor="#FFFFFF">
<p>Hi David,</p>
<p>The <span
style="box-sizing:border-box;color:rgb(36,41,46);font-family:-apple-system,system-ui,"Segoe
UI",Helvetica,Arial,sans-serif,"Apple
Color Emoji","Segoe UI
Emoji","Segoe UI
Symbol";font-size:16px;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;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"
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360final-path">NearestExonJB.pm
plugin is now available on github <a
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360moz-txt-link-freetext"
href="https://github.com/Ensembl/VEP_plugins"
target="_blank" moz-do-not-send="true">https://github.com/Ensembl/VEP_plugins</a>.
This plugin reports the nearest exon junction
boundary (exon id, bp distance, start or end, exon
length) within the affected transcript.</span></p>
<p><span
style="box-sizing:border-box;color:rgb(36,41,46);font-family:-apple-system,system-ui,"Segoe
UI",Helvetica,Arial,sans-serif,"Apple
Color Emoji","Segoe UI
Emoji","Segoe UI
Symbol";font-size:16px;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;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"
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360final-path">I
hope you find it useful.<br>
</span></p>
<p><span
style="box-sizing:border-box;color:rgb(36,41,46);font-family:-apple-system,system-ui,"Segoe
UI",Helvetica,Arial,sans-serif,"Apple
Color Emoji","Segoe UI
Emoji","Segoe UI
Symbol";font-size:16px;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;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"
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360final-path">Best
regards,</span></p>
<p><span
style="box-sizing:border-box;color:rgb(36,41,46);font-family:-apple-system,system-ui,"Segoe
UI",Helvetica,Arial,sans-serif,"Apple
Color Emoji","Segoe UI
Emoji","Segoe UI
Symbol";font-size:16px;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;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"
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360final-path">Irina</span><strong
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360final-path"
style="box-sizing:border-box;font-weight:600;color:rgb(36,41,46);font-family:-apple-system,system-ui,"Segoe
UI",Helvetica,Arial,sans-serif,"Apple
Color Emoji","Segoe UI
Emoji","Segoe UI
Symbol";font-size:16px;font-style:normal;font-variant-ligatures:normal;font-variant-caps:normal;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"><br>
</strong></p>
<div
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360moz-cite-prefix">On
25/02/2019 08:40, David Tamborero wrote:<br>
</div>
<blockquote type="cite">
<div dir="auto">That s fantastic, thanks!
<div dir="auto"><br>
</div>
<div dir="auto">Have a great week</div>
<div dir="auto">D</div>
</div>
<br>
<div class="gmail_quote">
<div dir="ltr" class="gmail_attr">El vie., 22 feb.
2019 17:48, Irina Armean <<a
href="mailto:iarmean@ebi.ac.uk" target="_blank"
moz-do-not-send="true">iarmean@ebi.ac.uk</a>>
escribió:<br>
</div>
<blockquote class="gmail_quote" style="margin:0px
0px 0px 0.8ex;border-left:1px solid
rgb(204,204,204);padding-left:1ex">
<div bgcolor="#FFFFFF">
<p>Hi David,</p>
<p>Thanks for the clarification and the positive
feedback for the team. We do our best to make
the desired functionality available in due
time, sometimes it's easier/faster than other
times.<br>
</p>
<p>We plan to add a VEP plugin within the next
week, which will report the nearest exon
junction boundary (exon id, bp distance, start
or end, exon length) for variants in the
protein coding region, this should answer your
case and also provide some additional use
cases.<br>
</p>
<p>For the case of frameshifts and premature
stop codons, they are handled more efficiently
in the main VEP code and is more complex to
update quickly however we plan to cover this
use case in the near future.</p>
<p>I will come back with a mail once the plugin
is in.<br>
</p>
<p>Best regards,</p>
<p>Irina<br>
</p>
<p><br>
</p>
<div
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767moz-cite-prefix">On
21/02/2019 17:17, David Tamborero wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">
<div dir="ltr">
<div>Hi Irina, thanks for your answer, it
is always awesome how diligent you are
guys; <br>
</div>
<div><br>
</div>
<div>my wishlist:</div>
<div><br>
</div>
<div>- in my case, what i m interested in
is in the distance (nucleotides) from my
variant 'within' the exon (ie protein
coding-affecting variant) to the next
exon junction. But note that other users
may be interested in other distances, as
those that you mention.</div>
<div><br>
</div>
<div>- FYI, i m interested in that info
for the variants that create preamture
stop codons, so I can estimate whether
it will be likely that the non-mediated
decay is triggered (which depends on how
far it falls regarding the last junction
of the transcript). Note that --for the
same reason-- I m also interested in,
given a frameshift mutation, where the
new 'cryptic' stop codon will be placed.
I currently calculate it by actually
using the VEP info that can be parsed
from the HGVSp column (e.g.
p.Glu5ValfsTer5, meaning the stop codon
in 5 codons after the first 'ectopic
codon' created by the frameshift, if I
remember well).</div>
<div><br>
</div>
<div>Again, I currently address both cases
by my own ad hoc scripts, but I thought
that you already 'have' the info to
easily output these things, which I
think it can be of interest for the
community (and surely more neat that my
creepy coding!)<br>
</div>
<div><br>
</div>
<div>hope it makes sense!</div>
<div>br</div>
<div>d<br>
</div>
</div>
</div>
<br>
<div class="gmail_quote">
<div dir="ltr" class="gmail_attr">El jue.,
21 feb. 2019 a las 17:12, Irina Armean
(<<a href="mailto:iarmean@ebi.ac.uk"
rel="noreferrer" target="_blank"
moz-do-not-send="true">iarmean@ebi.ac.uk</a>>)
escribió:<br>
</div>
<blockquote class="gmail_quote"
style="margin:0px 0px 0px
0.8ex;border-left:1px solid
rgb(204,204,204);padding-left:1ex">
<div bgcolor="#FFFFFF">
<p>Dear David,</p>
<p>Thanks for the question. We currently
don't have this functionality however
we can easily add the distance to the
closest exon.</p>
<p>To clarify, are you interested in
getting the distance to the nearest
exon junction for the variants only
when it affects a protein coding
transcript or also when they are
upstream/downstream of genes for
example?</p>
<p>Best regards,</p>
<p>Irina</p>
<p><br>
</p>
<div
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767gmail-m_-7639736395750451905moz-cite-prefix">On
21/02/2019 11:09, David Tamborero
wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">
<div>Dear all, <br>
</div>
<div><br>
</div>
<div>is any flag (which I cannot
find) so the VEP output includes
the distance of the (coding)
variant to the closest exon
junction?</div>
<div><br>
</div>
<div>If not, somebody has a
recommended fancy approach to do
so? (My current approach is 'just'
to match with my own script the
VEP output for a given transcript
with the exon coordinates data
that can be retrieved in e.g.
BioMart)</div>
<div><br>
</div>
<div>many thanks in advance!</div>
<div>d<br>
</div>
</div>
<br>
<fieldset
class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767gmail-m_-7639736395750451905mimeAttachmentHeader"></fieldset>
<pre class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767gmail-m_-7639736395750451905moz-quote-pre">_______________________________________________
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<pre class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767gmail-m_-7639736395750451905moz-signature" cols="72">--
Irina Armean PhD, Bioinformatican
Ensembl Variation, EMBL-EBI, Hinxton, UK
iarmean[at]<a href="http://ebi.ac.uk" rel="noreferrer" target="_blank" moz-do-not-send="true">ebi.ac.uk</a> | A3 - 135</pre>
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<pre class="gmail-m_-5727380057110329055gmail-m_3538932301546639360m_-16577229655441767moz-signature" cols="72">-- </pre>
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