NM_145206.4:c.264+18338T>G

Variant names:

• chr10-112482995-T-G
• rs2290966
• NM_145206.4:c.264+18338T>G

Variant summary

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

The NM_145206.4(VTI1A):​c.264+18338T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,808 control chromosomes in the GnomAD database, including 35,058 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 0.67 (35058 hom., cov: 31)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 0 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.264+18338T>G		intron_variant	Intron 3 of 7	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.264+18338T>G		intron_variant	Intron 3 of 7	2	NM_145206.4	ENSP00000376792.2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101774 AN: 151690 Hom.: 35025 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.671 AC: 101856 AN: 151808 Hom.: 35058 Cov.: 31 AF XY: 0.665 AC XY: 49315 AN XY: 74196

African (AFR) AF: 0.699 AC: 28919 AN: 41392

American (AMR) AF: 0.562 AC: 8569 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2491 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1264 AN: 5132

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4810

European-Finnish (FIN) AF: 0.736 AC: 7737 AN: 10514

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48310 AN: 67940

Other (OTH) AF: 0.660 AC: 1392 AN: 2110

Alfa AF: 0.668 Hom.: 15483

Bravo AF: 0.654

Asia WGS AF: 0.389 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		0.51
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: rs2290966; hg19: chr10-114242754;