10-49016721-C-T

Position:

• chr10-49016721-C-T

Variant summary

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

The NM_001031746.5(VSTM4):​c.*2929G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,208 control chromosomes in the GnomAD database, including 36,614 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 (36613 hom., cov: 34)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: VSTM4 NM_001031746.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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.*2929G>A		3_prime_UTR_variant	8/8	ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.*3041G>A		3_prime_UTR_variant	9/9		XP_016871316.1
VSTM4	XM_047424711.1	c.*3041G>A		3_prime_UTR_variant	9/9		XP_047280667.1
VSTM4	XR_001747052.3	n.3370G>A		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.*2929G>A		3_prime_UTR_variant	8/8	1	NM_001031746.5	ENSP00000331062	P1
	ENST00000422966.1	n.403-2105C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102845 AN: 152086 Hom.: 36610 Cov.: 34

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.676 AC: 102880 AN: 152204 Hom.: 36613 Cov.: 34 AF XY: 0.672 AC XY: 49974 AN XY: 74406

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.694

Alfa AF: 0.776 Hom.: 55336

Bravo AF: 0.661

Asia WGS AF: 0.548 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.51

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: rs2244967; hg19: chr10-50224766;