NM_001031746.5:c.458-602C>T

Variant names:

• chr10-49086625-G-A
• rs4317904
• NM_001031746.5:c.458-602C>T

Variant summary

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

The NM_001031746.5(VSTM4):​c.458-602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,156 control chromosomes in the GnomAD database, including 37,606 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 0.69 (37606 hom., cov: 33)
• Consequence: VSTM4 NM_001031746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM4	NM_001031746.5	c.458-602C>T		intron_variant	Intron 2 of 7	ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.458-602C>T		intron_variant	Intron 2 of 8		XP_016871316.1
VSTM4	XM_047424711.1	c.458-602C>T		intron_variant	Intron 2 of 8		XP_047280667.1
VSTM4	XR_001747052.3	n.495-602C>T		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.458-602C>T		intron_variant	Intron 2 of 7	1	NM_001031746.5	ENSP00000331062.3

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104381 AN: 152038 Hom.: 37542 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.687 AC: 104509 AN: 152156 Hom.: 37606 Cov.: 33 AF XY: 0.685 AC XY: 50909 AN XY: 74362

African (AFR) AF: 0.907 AC: 37677 AN: 41542

American (AMR) AF: 0.614 AC: 9384 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1493 AN: 5174

South Asian (SAS) AF: 0.713 AC: 3429 AN: 4812

European-Finnish (FIN) AF: 0.605 AC: 6395 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41724 AN: 67990

Other (OTH) AF: 0.662 AC: 1392 AN: 2104

Alfa AF: 0.639 Hom.: 22901

Bravo AF: 0.688

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.6
DANN	Benign	0.48
PhyloP100		0.65
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: rs4317904; hg19: chr10-50294670;