rs17175928

chr10-49089520-C-A

Variant summary

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

The NM_001031746.5(VSTM4):c.458-3497G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 152,216 control chromosomes in the GnomAD database, including 939 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 0.096 (939 hom., cov: 33)
• Consequence: VSTM4 NM_001031746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSTM4	NM_001031746.5	c.458-3497G>T		intron_variant		ENST00000332853.9
VSTM4	XM_017015827.3	c.458-3497G>T		intron_variant
VSTM4	XM_047424711.1	c.458-3497G>T		intron_variant
VSTM4	XR_001747052.3	n.495-3497G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM4	ENST00000332853.9	c.458-3497G>T		intron_variant		1	NM_001031746.5	P1

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14614 AN: 152098 Hom.: 939 Cov.: 33

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0960 AC: 14618 AN: 152216 Hom.: 939 Cov.: 33 AF XY: 0.0994 AC XY: 7395 AN XY: 74416

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0476

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.0970 Hom.: 162

Bravo AF: 0.103

Asia WGS AF: 0.209 AC: 724 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	0.92
Dann	Benign	0.58

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: rs17175928; hg19: chr10-50297565;