rs1022907

Variant names:

• chr10-112635035-C-T
• rs1022907
• NM_145206.4:c.428-33183C>T

Variant summary

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

The NM_145206.4(VTI1A):​c.428-33183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,070 control chromosomes in the GnomAD database, including 7,095 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 0.30 (7095 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	NM_145206.4	MANE Select	c.428-33183C>T		intron	N/A	NP_660207.2
	VTI1A	NM_001318203.2		c.449-33183C>T		intron	N/A	NP_001305132.1
	VTI1A	NM_001365711.1		c.449-33183C>T		intron	N/A	NP_001352640.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	ENST00000393077.3	TSL:2 MANE Select	c.428-33183C>T		intron	N/A	ENSP00000376792.2
	VTI1A	ENST00000432306.5	TSL:1	c.428-33183C>T		intron	N/A	ENSP00000395017.1
	VTI1A	ENST00000705995.1		c.449-33183C>T		intron	N/A	ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45591 AN: 151952 Hom.: 7091 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.300 AC: 45601 AN: 152070 Hom.: 7095 Cov.: 32 AF XY: 0.297 AC XY: 22102 AN XY: 74314

African (AFR) AF: 0.232 AC: 9626 AN: 41482

American (AMR) AF: 0.317 AC: 4848 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3466

East Asian (EAS) AF: 0.350 AC: 1812 AN: 5174

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3606 AN: 10554

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22407 AN: 67988

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.320 Hom.: 35374

Bravo AF: 0.297

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		-0.27
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: rs1022907; hg19: chr10-114394794;