rs7088368

Positions:

• chr10-112699170-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145206.4(VTI1A):​c.560+30172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,210 control chromosomes in the GnomAD database, including 14,073 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 0.38 (14073 hom., cov: 33)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.560+30172A>G		intron_variant		ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.560+30172A>G		intron_variant		2	NM_145206.4	ENSP00000376792	P4
VTI1A	ENST00000432306.5	c.560+30172A>G		intron_variant		1		ENSP00000395017
VTI1A	ENST00000705995.1	c.581+30172A>G		intron_variant				ENSP00000516199	A1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57992 AN: 152092 Hom.: 14029 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.382 AC: 58089 AN: 152210 Hom.: 14073 Cov.: 33 AF XY: 0.376 AC XY: 27955 AN XY: 74428

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.370

Alfa AF: 0.282 Hom.: 10641

Bravo AF: 0.412

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.75

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: rs7088368; hg19: chr10-114458929;