chr10-112745706-G-A

Variant names:

• chr10-112745706-G-A
• rs7918405
• NM_145206.4:c.561-69584G>A

Variant summary

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

The NM_145206.4(VTI1A):​c.561-69584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,108 control chromosomes in the GnomAD database, including 15,418 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 0.40 (15418 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.561-69584G>A		intron_variant	Intron 7 of 7	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.561-69584G>A		intron_variant	Intron 7 of 7	2	NM_145206.4	ENSP00000376792.2
VTI1A	ENST00000705995.1	c.582-69584G>A		intron_variant	Intron 8 of 8			ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60149 AN: 151990 Hom.: 15375 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.396 AC: 60245 AN: 152108 Hom.: 15418 Cov.: 32 AF XY: 0.390 AC XY: 29003 AN XY: 74382

African (AFR) AF: 0.732 AC: 30372 AN: 41500

American (AMR) AF: 0.330 AC: 5047 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2570 AN: 5168

South Asian (SAS) AF: 0.228 AC: 1096 AN: 4812

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10590

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17321 AN: 67980

Other (OTH) AF: 0.379 AC: 800 AN: 2110

Alfa AF: 0.304 Hom.: 32429

Bravo AF: 0.428

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.13
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: rs7918405; hg19: chr10-114505465;