10-112598796-C-T

Variant names:

• chr10-112598796-C-T
• rs1325172
• NM_145206.4:c.427+60466C>T

Variant summary

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

The NM_145206.4(VTI1A):​c.427+60466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,192 control chromosomes in the GnomAD database, including 52,491 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 0.82 (52491 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 7 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]

LOC124902503 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.427+60466C>T		intron_variant	Intron 5 of 7	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.427+60466C>T		intron_variant	Intron 5 of 7	2	NM_145206.4	ENSP00000376792.2
VTI1A	ENST00000432306.5	c.427+60466C>T		intron_variant	Intron 5 of 7	1		ENSP00000395017.1
VTI1A	ENST00000705995.1	c.448+60466C>T		intron_variant	Intron 6 of 8			ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125384 AN: 152074 Hom.: 52428 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.825 AC: 125504 AN: 152192 Hom.: 52491 Cov.: 32 AF XY: 0.816 AC XY: 60703 AN XY: 74418

African (AFR) AF: 0.936 AC: 38861 AN: 41518

American (AMR) AF: 0.841 AC: 12861 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2778 AN: 5170

South Asian (SAS) AF: 0.598 AC: 2882 AN: 4816

European-Finnish (FIN) AF: 0.769 AC: 8145 AN: 10586

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54960 AN: 68018

Other (OTH) AF: 0.801 AC: 1690 AN: 2110

Alfa AF: 0.807 Hom.: 212810

Bravo AF: 0.839

Asia WGS AF: 0.561 AC: 1954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.20
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: rs1325172; hg19: chr10-114358555;