NM_145206.4:c.95-3029G>A

Variant names:

• chr10-112457495-G-A
• rs7917657
• NM_145206.4:c.95-3029G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145206.4(VTI1A):​c.95-3029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,114 control chromosomes in the GnomAD database, including 56,215 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (56215 hom., cov: 31)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 4 publications found

Genes affected

VTI1A (HGNC:17792): (vesicle transport through interaction with t-SNAREs 1A) The protein encoded by this gene is a member of the family of soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNAREs) that function in intracellular trafficking. This family member is involved in vesicular transport between endosomes and the trans-Golgi network. It is a vesicle-associated SNARE (v-SNARE) that interacts with target membrane SNAREs (t-SNAREs). Polymorphisms in this gene have been associated with binocular function, and also with susceptibility to colorectal and lung cancers. A recurrent rearrangement has been found between this gene and the transcription factor 7-like 2 (TCF7L2) gene in colorectal cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.95-3029G>A		intron_variant	Intron 1 of 7	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.95-3029G>A		intron_variant	Intron 1 of 7	2	NM_145206.4	ENSP00000376792.2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129389 AN: 151996 Hom.: 56181 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.851 AC: 129477 AN: 152114 Hom.: 56215 Cov.: 31 AF XY: 0.843 AC XY: 62713 AN XY: 74372

African (AFR) AF: 0.862 AC: 35763 AN: 41466

American (AMR) AF: 0.735 AC: 11228 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1840 AN: 5158

South Asian (SAS) AF: 0.635 AC: 3056 AN: 4812

European-Finnish (FIN) AF: 0.904 AC: 9580 AN: 10594

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62276 AN: 68016

Other (OTH) AF: 0.841 AC: 1777 AN: 2114

Alfa AF: 0.880 Hom.: 141579

Bravo AF: 0.833

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.32
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7917657; hg19: chr10-114217254;