10-112816994-C-T

Variant names:

• chr10-112816994-C-T
• rs1047468
• NM_145206.4:c.*1611C>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.*1611C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 231,462 control chromosomes in the GnomAD database, including 8,038 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 0.23 (4629 hom., cov: 32)
  • Exomes 𝑓: 0.28 (3409 hom.)
• Consequence: VTI1A NM_145206.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 7 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]

ENSG00000285676 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.502 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	NM_145206.4	MANE Select	c.*1611C>T		3_prime_UTR	Exon 8 of 8	NP_660207.2	Q96AJ9-2
	VTI1A	NM_001318203.2		c.*1611C>T		3_prime_UTR	Exon 9 of 9	NP_001305132.1	A0A994J5N6
	VTI1A	NM_001365712.1		c.*1712C>T		3_prime_UTR	Exon 9 of 9	NP_001352641.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	ENST00000393077.3	TSL:2 MANE Select	c.*1611C>T		3_prime_UTR	Exon 8 of 8	ENSP00000376792.2	Q96AJ9-2
	VTI1A	ENST00000705995.1		c.*1611C>T		3_prime_UTR	Exon 9 of 9	ENSP00000516199.1	A0A994J5N6
	VTI1A	ENST00000876660.1		c.*1611C>T		3_prime_UTR	Exon 7 of 7	ENSP00000546719.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34201 AN: 151862 Hom.: 4628 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.277 AC: 22013 AN: 79482 Hom.: 3409 Cov.: 0 AF XY: 0.279 AC XY: 10202 AN XY: 36558

African (AFR) AF: 0.0946 AC: 362 AN: 3826

American (AMR) AF: 0.237 AC: 582 AN: 2452

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 1191 AN: 5034

East Asian (EAS) AF: 0.457 AC: 5103 AN: 11176

South Asian (SAS) AF: 0.448 AC: 308 AN: 688

European-Finnish (FIN) AF: 0.197 AC: 13 AN: 66

Middle Eastern (MID) AF: 0.209 AC: 102 AN: 488

European-Non Finnish (NFE) AF: 0.258 AC: 12665 AN: 49102

Other (OTH) AF: 0.254 AC: 1687 AN: 6650

GnomAD4 genome AF: 0.225 AC: 34211 AN: 151980 Hom.: 4629 Cov.: 32 AF XY: 0.229 AC XY: 17003 AN XY: 74278

African (AFR) AF: 0.0984 AC: 4075 AN: 41426

American (AMR) AF: 0.243 AC: 3720 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2674 AN: 5158

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4816

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10558

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17804 AN: 67962

Other (OTH) AF: 0.222 AC: 467 AN: 2100

Alfa AF: 0.251 Hom.: 8235

Bravo AF: 0.218

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1047468; hg19: chr10-114576753;