rs736597

Positions:

• chr10-112552778-T-A
• chr10-112552778-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145206.4(VTI1A):​c.427+14448T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 152,306 control chromosomes in the GnomAD database, including 378 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 0.043 (378 hom., cov: 32)
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.427+14448T>A		intron_variant		ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.427+14448T>A		intron_variant		2	NM_145206.4	ENSP00000376792	P4
VTI1A	ENST00000432306.5	c.427+14448T>A		intron_variant		1		ENSP00000395017
VTI1A	ENST00000705995.1	c.448+14448T>A		intron_variant				ENSP00000516199	A1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6539 AN: 152188 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0430 AC: 6550 AN: 152306 Hom.: 378 Cov.: 32 AF XY: 0.0476 AC XY: 3545 AN XY: 74486

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0313 Hom.: 15

Bravo AF: 0.0397

Asia WGS AF: 0.279 AC: 965 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.77

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: rs736597; hg19: chr10-114312537;