Uncorrect impact of inversion

[Artemlin6231]

Describe the issue

We investigated how vep annotates inversions and performed an inversion in the vcf file on the region chr17:7671525-7685229, where vep was expected to assign a HIGH impact to this inversion since it encompasses the exons of the TP53 gene. However, vep assigned it a MODIFIER status.

System

• VEP version: 110

Full VEP command line

vep -i /mnt/hetero.vcf --gff /mnt_hg38/hg38.annotation.gff3.gz --fasta /mnt_hg38/hg38.fa -o hetero -q --tab --symbol --max_sv_size 1000000

[likhitha-surapaneni]

Hi @Artemlin6231 , thank you for investigating. Can you please provide us with the input file used?

[Artemlin6231]

input file contained the line chr17 7671524 2427 N 371.6 . SVTYPE=INV;SVLEN=13705;END=7685229;STRANDS=++:1,--:10;IMPRECISE;CIPOS=-27,27;CIEND=-246,29;CIPOS95=-10,5;CIEND95=-94,1;SU=29 ...

[likhitha-surapaneni]

Hi @Artemlin6231 , thank you for providing us with the input file. VEP currently assigns IMPACT as per this table. Could you please elaborate on the expected output and which transcripts should instead have a HIGH impact?

[Artemlin6231]

Hi!
I expected to see a HIGH impact because the inversion intersects with several exons of the functionally significant TP53 gene. I am attaching a screenshot indicating the location of this inversion, and a file where I annotated the inversions using VEP

[output_invers.txt](https://github.com/Ensembl/ensembl-vep/files/14725343/output_invers.txt)