rs4918762

Variant names:

• chr10-112639347-A-T
• rs4918762
• NM_145206.4:c.428-28871A>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.428-28871A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,046 control chromosomes in the GnomAD database, including 22,367 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 0.52 (22367 hom., cov: 33)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 2 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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	NM_145206.4	MANE Select	c.428-28871A>T		intron	N/A	NP_660207.2
	VTI1A	NM_001318203.2		c.449-28871A>T		intron	N/A	NP_001305132.1
	VTI1A	NM_001365711.1		c.449-28871A>T		intron	N/A	NP_001352640.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	ENST00000393077.3	TSL:2 MANE Select	c.428-28871A>T		intron	N/A	ENSP00000376792.2
	VTI1A	ENST00000432306.5	TSL:1	c.428-28871A>T		intron	N/A	ENSP00000395017.1
	VTI1A	ENST00000705995.1		c.449-28871A>T		intron	N/A	ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78631 AN: 151928 Hom.: 22375 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.517 AC: 78625 AN: 152046 Hom.: 22367 Cov.: 33 AF XY: 0.508 AC XY: 37772 AN XY: 74300

African (AFR) AF: 0.331 AC: 13751 AN: 41490

American (AMR) AF: 0.414 AC: 6326 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1970 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1389 AN: 5182

South Asian (SAS) AF: 0.384 AC: 1854 AN: 4824

European-Finnish (FIN) AF: 0.665 AC: 7022 AN: 10556

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44227 AN: 67932

Other (OTH) AF: 0.513 AC: 1082 AN: 2110

Alfa AF: 0.573 Hom.: 3243

Bravo AF: 0.491

Asia WGS AF: 0.284 AC: 988 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.0
DANN	Benign	0.53
PhyloP100		1.2
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: rs4918762; hg19: chr10-114399106;