10-112747837-G-A

Variant names:

• chr10-112747837-G-A
• rs7070850
• NM_145206.4:c.561-67453G>A

Variant summary

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

The NM_001318203.2(VTI1A):​c.582-67453G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,098 control chromosomes in the GnomAD database, including 75 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 0.017 (75 hom., cov: 32)
• Consequence: VTI1A NM_001318203.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318203.2. 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.561-67453G>A		intron	N/A	NP_660207.2
	VTI1A	NM_001318203.2		c.582-67453G>A		intron	N/A	NP_001305132.1
	VTI1A	NM_001365711.1		c.581+78839G>A		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.561-67453G>A		intron	N/A	ENSP00000376792.2
	VTI1A	ENST00000705995.1		c.582-67453G>A		intron	N/A	ENSP00000516199.1
	VTI1A	ENST00000876660.1		c.483-67453G>A		intron	N/A	ENSP00000546719.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2557 AN: 151980 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0168 AC: 2562 AN: 152098 Hom.: 75 Cov.: 32 AF XY: 0.0162 AC XY: 1205 AN XY: 74362

African (AFR) AF: 0.0586 AC: 2429 AN: 41462

American (AMR) AF: 0.00582 AC: 89 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67992

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.00 Hom.: 210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.39
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

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: rs7070850; hg19: chr10-114507596;