10-49086625-G-A

Position:

• chr10-49086625-G-A

Variant summary

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

The ENST00000332853.9(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 ENST00000332853.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653

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=-0.97).
• 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/exons	MANE	Protein	UniProt
VSTM4	NM_001031746.5	c.458-602C>T		intron_variant		ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.458-602C>T		intron_variant			XP_016871316.1
VSTM4	XM_047424711.1	c.458-602C>T		intron_variant			XP_047280667.1
VSTM4	XR_001747052.3	n.495-602C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.458-602C>T		intron_variant		1	NM_001031746.5	ENSP00000331062	P1

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

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.662

Alfa AF: 0.637 Hom.: 18747

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

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: rs4317904; hg19: chr10-50294670;