chr1-212953223-G-A

Position:

• chr1-212953223-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001301056.2(VASH2):​c.276+1405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 146,732 control chromosomes in the GnomAD database, including 10,916 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 0.36 (10916 hom., cov: 31)
• Consequence: VASH2 NM_001301056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

Genes affected

VASH2 (HGNC:25723): (vasohibin 2) Enables actin binding activity; metallocarboxypeptidase activity; and microtubule binding activity. Involved in axon development and proteolysis. Acts upstream of or within cell-cell fusion; positive regulation of angiogenesis; and positive regulation of endothelial cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VASH2	NM_001301056.2	c.276+1405G>A		intron_variant		ENST00000517399.3
VASH2	NM_001136474.3	c.81+1405G>A		intron_variant
VASH2	NM_001136475.3	c.-37+2483G>A		intron_variant
VASH2	NM_024749.5	c.276+1405G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VASH2	ENST00000517399.3	c.276+1405G>A		intron_variant		1	NM_001301056.2	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 52447 AN: 146612 Hom.: 10921 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.305

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.357 AC: 52433 AN: 146732 Hom.: 10916 Cov.: 31 AF XY: 0.358 AC XY: 25637 AN XY: 71686

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.359

Alfa AF: 0.398 Hom.: 1749

Bravo AF: 0.322

Asia WGS AF: 0.427 AC: 1482 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3002288; hg19: chr1-213126565;