10-112719503-G-T

Variant names:

• chr10-112719503-G-T
• rs7342028
• NM_145206.4:c.560+50505G>T

Variant summary

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

The NM_145206.4(VTI1A):​c.560+50505G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,500 control chromosomes in the GnomAD database, including 10,082 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 0.34 (10082 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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 = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.560+50505G>T		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.560+50505G>T		intron_variant	Intron 7 of 7	2	NM_145206.4	ENSP00000376792.2
VTI1A	ENST00000432306.5	c.561-17220G>T		intron_variant	Intron 7 of 7	1		ENSP00000395017.1
VTI1A	ENST00000705995.1	c.581+50505G>T		intron_variant	Intron 8 of 8			ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51130 AN: 151402 Hom.: 10060 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.338 AC: 51202 AN: 151500 Hom.: 10082 Cov.: 32 AF XY: 0.334 AC XY: 24743 AN XY: 73998

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.336

Alfa AF: 0.264 Hom.: 5909

Bravo AF: 0.363

Asia WGS AF: 0.380 AC: 1321 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	0.39
DANN	Benign	0.42

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: rs7342028; hg19: chr10-114479262;