chr10-112670447-C-A

Variant names:

• chr10-112670447-C-A
• rs11814680
• NM_145206.4:c.560+1449C>A

Variant summary

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

The NM_145206.4(VTI1A):​c.560+1449C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,062 control chromosomes in the GnomAD database, including 6,832 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 0.24 (6832 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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.560+1449C>A		intron	N/A	NP_660207.2	Q96AJ9-2
	VTI1A	NM_001318203.2		c.581+1449C>A		intron	N/A	NP_001305132.1	A0A994J5N6
	VTI1A	NM_001365711.1		c.581+1449C>A		intron	N/A	NP_001352640.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	ENST00000393077.3	TSL:2 MANE Select	c.560+1449C>A		intron	N/A	ENSP00000376792.2	Q96AJ9-2
	VTI1A	ENST00000432306.5	TSL:1	c.560+1449C>A		intron	N/A	ENSP00000395017.1	Q96AJ9-1
	VTI1A	ENST00000705995.1		c.581+1449C>A		intron	N/A	ENSP00000516199.1	A0A994J5N6

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36908 AN: 151944 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152062 Hom.: 6832 Cov.: 32 AF XY: 0.236 AC XY: 17567 AN XY: 74336

African (AFR) AF: 0.524 AC: 21694 AN: 41438

American (AMR) AF: 0.158 AC: 2403 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5178

South Asian (SAS) AF: 0.117 AC: 564 AN: 4824

European-Finnish (FIN) AF: 0.0870 AC: 922 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9655 AN: 67980

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.173 Hom.: 4379

Bravo AF: 0.262

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.48
PhyloP100		2.2
Mutation Taster		=99/1	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: rs11814680; hg19: chr10-114430206; COSMIC: COSV67580788; COSMIC: COSV67580788;