rs17267338

Variant names:

• chr10-112628513-A-G
• rs17267338
• NM_145206.4:c.428-39705A>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.428-39705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,274 control chromosomes in the GnomAD database, including 269 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 0.051 (269 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 6 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.428-39705A>G		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.428-39705A>G		intron_variant	Intron 5 of 7	2	NM_145206.4	ENSP00000376792.2
VTI1A	ENST00000432306.5	c.428-39705A>G		intron_variant	Intron 5 of 7	1		ENSP00000395017.1
VTI1A	ENST00000705995.1	c.449-39705A>G		intron_variant	Intron 6 of 8			ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7823 AN: 152156 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0537

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0514 AC: 7823 AN: 152274 Hom.: 269 Cov.: 32 AF XY: 0.0511 AC XY: 3806 AN XY: 74452

African (AFR) AF: 0.0136 AC: 566 AN: 41580

American (AMR) AF: 0.0433 AC: 662 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 186 AN: 3466

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5184

South Asian (SAS) AF: 0.0507 AC: 244 AN: 4814

European-Finnish (FIN) AF: 0.0695 AC: 737 AN: 10610

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0769 AC: 5231 AN: 68002

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0640 Hom.: 427

Bravo AF: 0.0469

Asia WGS AF: 0.0350 AC: 120 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		1.7
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: rs17267338; hg19: chr10-114388272;