rs2137920

Positions:

• chr10-49021593-T-A
• chr10-49021593-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031746.5(VSTM4):​c.838-1818A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,958 control chromosomes in the GnomAD database, including 36,601 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 0.68 (36601 hom., cov: 31)
• Consequence: VSTM4 NM_001031746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

VSTM4 (HGNC:26470): (V-set and transmembrane domain containing 4) Predicted to act upstream of or within several processes, including endothelial cell migration; retina blood vessel maintenance; and vasculature development. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM4	NM_001031746.5	c.838-1818A>T		intron_variant		ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.998-1818A>T		intron_variant			XP_016871316.1
VSTM4	XM_047424711.1	c.983-1818A>T		intron_variant			XP_047280667.1
VSTM4	XR_001747052.3	n.875-1818A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.838-1818A>T		intron_variant		1	NM_001031746.5	ENSP00000331062	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102789 AN: 151842 Hom.: 36598 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.677 AC: 102824 AN: 151958 Hom.: 36601 Cov.: 31 AF XY: 0.672 AC XY: 49959 AN XY: 74298

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.695

Alfa AF: 0.739 Hom.: 5326

Bravo AF: 0.662

Asia WGS AF: 0.548 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2137920; hg19: chr10-50229638;