rs1408817

Variant names:

• chr10-112738386-A-G
• rs1408817
• NM_145206.4:c.560+69388A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-112738386-A-G
• chr10-112738386-A-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.560+69388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,106 control chromosomes in the GnomAD database, including 40,154 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 0.72 (40154 hom., cov: 31)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 9 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 = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4	c.560+69388A>G		intron_variant	Intron 7 of 7	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.560+69388A>G		intron_variant	Intron 7 of 7	2	NM_145206.4	ENSP00000376792.2
VTI1A	ENST00000705995.1	c.581+69388A>G		intron_variant	Intron 8 of 8			ENSP00000516199.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109488 AN: 151988 Hom.: 40100 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.721 AC: 109593 AN: 152106 Hom.: 40154 Cov.: 31 AF XY: 0.714 AC XY: 53102 AN XY: 74344

African (AFR) AF: 0.850 AC: 35319 AN: 41532

American (AMR) AF: 0.742 AC: 11342 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2425 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4457 AN: 5144

South Asian (SAS) AF: 0.511 AC: 2463 AN: 4816

European-Finnish (FIN) AF: 0.631 AC: 6660 AN: 10560

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44773 AN: 67974

Other (OTH) AF: 0.723 AC: 1527 AN: 2112

Alfa AF: 0.682 Hom.: 61861

Bravo AF: 0.744

Asia WGS AF: 0.681 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		0.079
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: rs1408817; hg19: chr10-114498145;