<p>I am trying to reproduce an analysis result, and there is a requirement regarding the format of the result: the '3' rule ': all mutations should be expressed in a position close to the end of the gene transcription direction (3' end).</p>
<p>The result I obtained is(annotate from VEP)</p>
<pre><code>Chromosome  Start_Position  End_Position    Strand  Variant_Classification  Variant_Type    Reference_Allele    Tumor_Seq_Allele1   Tumor_Seq_Allele2   HGVSc   HGVSp   HGVSp_Short Transcript_ID
10  89692835    89692840    +   In_Frame_Del    DEL GATCTT  GATCTT  -   c.321_326del    p.Leu108_Asp109del  p.L108_D109del  NM_000314.8

</code></pre>
<p>the standard answer</p>
<pre><code>chr10   89692837    89692842    TCTTGA      PTEN    NM_00314    c.321_326del    p.Leu108_Asp109del
</code></pre>
<p>I speculate that ：
the HGVS standard followed by VEP includes the 3'rule . So ultimately, there is the same <code>p.Leu108_ Asp109del</code>。 But the output of vep did not adjust Start_ Position and End_ Position？（Perhaps it thinks that after obtaining the correct amino acid mutation , it doesn't matter anymore）
But for me, I hope the ultimate Start_ Position and End_ The Position also complies with the regulations, which seems a bit troublesome because the different  transcripts may have different directions and always rely on the IGV to correct it , which is also tiring.</p>
<p>Thanks for any suggestions</p>
<hr />
<p><a href="https://i.sstatic.net/Eyk9F.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/Eyk9F.png" alt="enter image description here" /></a></p>
<p>I have added an IGV image to better illustrate the problem. Reference genome regions 89692830 to 89692845 for the example in the figure.
bwa(or other software，like bowtie2) believes that the position of del should be</p>
<pre><code>ref:GTGAAGATCTTGACCA
alt:GTGAA------GACCA
</code></pre>
<p>But 3'rule believes that the position of del should be</p>
<pre><code>ref:GTGAAGATCTTGACCA
alt:GTGAAGA------CCA
</code></pre>
<p>To verify whether the results match 3'rule, it is necessary to know the direction of the transcripts, and each gene always has multiple transcripts, which is where I am confused</p>

CC BY-SA 4.0
2023-05-19T14:28:22.220Z
Thanks for the update @tanqiang
M__
CC BY-SA 4.0
2023-05-19T17:19:50.627Z
Can you clarify which representation you need? Is it the genomic level, the coding level or the protein level? Also, what is the input here? Do you start with variants or with VEP output? How many do you have? Do you only want to get one result, or does this need to be automated? Why are other transcripts relevant if you already have `NM_000314.8`?
terdon
<indel><vep>
How to normalise indel of different transcript direction?
# How to normalise indel of different transcript direction?

(Asked by: username_0 on 2023-05-19)

I am trying to reproduce an analysis result, and there is a requirement regarding the format of the result: the '3' rule ': all mutations should be expressed in a position close to the end of the gene transcription direction (3' end).
The result I obtained is(annotate from VEP)
Chromosome  Start_Position  End_Position    Strand  Variant_Classification  Variant_Type    Reference_Allele    Tumor_Seq_Allele1   Tumor_Seq_Allele2   HGVSc   HGVSp   HGVSp_Short Transcript_ID
10  89692835    89692840    +   In_Frame_Del    DEL GATCTT  GATCTT  -   c.321_326del    p.Leu108_Asp109del  p.L108_D109del  NM_000314.8


the standard answer
chr10   89692837    89692842    TCTTGA      PTEN    NM_00314    c.321_326del    p.Leu108_Asp109del

I speculate that ：
the HGVS standard followed by VEP includes the 3'rule . So ultimately, there is the same p.Leu108_ Asp109del。 But the output of vep did not adjust Start_ Position and End_ Position？（Perhaps it thinks that after obtaining the correct amino acid mutation , it doesn't matter anymore）
But for me, I hope the ultimate Start_ Position and End_ The Position also complies with the regulations, which seems a bit troublesome because the different  transcripts may have different directions and always rely on the IGV to correct it , which is also tiring.
Thanks for any suggestions


I have added an IGV image to better illustrate the problem. Reference genome regions 89692830 to 89692845 for the example in the figure.
bwa(or other software，like bowtie2) believes that the position of del should be
ref:GTGAAGATCTTGACCA
alt:GTGAA------GACCA

But 3'rule believes that the position of del should be
ref:GTGAAGATCTTGACCA
alt:GTGAAGA------CCA

To verify whether the results match 3'rule, it is necessary to know the direction of the transcripts, and each gene always has multiple transcripts, which is where I am confused

**Tags:** indel, vep
> **Comments:**
> **username_1**: Thanks for the update @tanqiang  
> **username_2**: Can you clarify which representation you need? Is it the genomic level, the coding level or the protein level? Also, what is the input here? Do you start with variants or with VEP output? How many do you have? Do you only want to get one result, or does this need to be automated? Why are other transcripts relevant if you already have `NM_000314.8`?  

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## 0 answers

