chr10-112756614-T-C

Variant names:

• chr10-112756614-T-C
• rs7068695
• NM_145206.4:c.561-58676T>C

Variant summary

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

The NM_145206.4(VTI1A):​c.561-58676T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,060 control chromosomes in the GnomAD database, including 9,604 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 0.35 (9604 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 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.561-58676T>C		intron	N/A	NP_660207.2	Q96AJ9-2
	VTI1A	NM_001318203.2		c.582-58676T>C		intron	N/A	NP_001305132.1	A0A994J5N6
	VTI1A	NM_001365711.1		c.581+87616T>C		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.561-58676T>C		intron	N/A	ENSP00000376792.2	Q96AJ9-2
	VTI1A	ENST00000705995.1		c.582-58676T>C		intron	N/A	ENSP00000516199.1	A0A994J5N6
	VTI1A	ENST00000876660.1		c.483-58676T>C		intron	N/A	ENSP00000546719.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52496 AN: 151942 Hom.: 9589 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.346 AC: 52563 AN: 152060 Hom.: 9604 Cov.: 32 AF XY: 0.343 AC XY: 25507 AN XY: 74326

African (AFR) AF: 0.440 AC: 18246 AN: 41480

American (AMR) AF: 0.369 AC: 5639 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2715 AN: 5152

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4810

European-Finnish (FIN) AF: 0.198 AC: 2093 AN: 10590

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20280 AN: 67974

Other (OTH) AF: 0.360 AC: 761 AN: 2114

Alfa AF: 0.313 Hom.: 6827

Bravo AF: 0.366

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.68
PhyloP100		-1.2
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: rs7068695; hg19: chr10-114516373;