rs4918762

chr10-112639347-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VTI1A	NM_145206.4	c.428-28871A>T		intron_variant		ENST00000393077.3
LOC124902503	XR_007062292.1	n.40292A>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTI1A	ENST00000393077.3	c.428-28871A>T		intron_variant		2	NM_145206.4	P4
VTI1A	ENST00000432306.5	c.428-28871A>T		intron_variant		1
VTI1A	ENST00000705995.1	c.449-28871A>T		intron_variant				A1

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.513

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	8.0
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs4918762; hg19: chr10-114399106;