rs10508911

Variant names:

• chr10-49098341-C-T
• rs10508911
• NM_001031746.5:c.457+9253G>A

Variant summary

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

The NM_001031746.5(VSTM4):​c.457+9253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,224 control chromosomes in the GnomAD database, including 2,376 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 0.17 (2376 hom., cov: 32)
• Consequence: VSTM4 NM_001031746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM4	NM_001031746.5	c.457+9253G>A		intron_variant	Intron 2 of 7	ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.457+9253G>A		intron_variant	Intron 2 of 8		XP_016871316.1
VSTM4	XM_047424711.1	c.457+9253G>A		intron_variant	Intron 2 of 8		XP_047280667.1
VSTM4	XR_001747052.3	n.494+9253G>A		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.457+9253G>A		intron_variant	Intron 2 of 7	1	NM_001031746.5	ENSP00000331062.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25558 AN: 152106 Hom.: 2372 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.168 AC: 25562 AN: 152224 Hom.: 2376 Cov.: 32 AF XY: 0.163 AC XY: 12102 AN XY: 74426

African (AFR) AF: 0.121 AC: 5035 AN: 41520

American (AMR) AF: 0.145 AC: 2225 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.146 AC: 704 AN: 4826

European-Finnish (FIN) AF: 0.130 AC: 1384 AN: 10610

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14770 AN: 68000

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.205 Hom.: 5631

Bravo AF: 0.168

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.82
PhyloP100		0.57
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: rs10508911; hg19: chr10-50306386;