rs12245255

Positions:

• chr10-49107035-C-G

Variant summary

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

The NM_001031746.5(VSTM4):​c.457+559G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,166 control chromosomes in the GnomAD database, including 5,762 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 0.24 (5762 hom., cov: 33)
• Consequence: VSTM4 NM_001031746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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]

VSTM4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM4	NM_001031746.5	c.457+559G>C		intron_variant		ENST00000332853.9	NP_001026916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.457+559G>C		intron_variant		1	NM_001031746.5	ENSP00000331062.3
VSTM4	ENST00000298454.3	c.457+559G>C		intron_variant		2		ENSP00000298454.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36312 AN: 152048 Hom.: 5760 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.239 AC: 36344 AN: 152166 Hom.: 5762 Cov.: 33 AF XY: 0.239 AC XY: 17804 AN XY: 74398

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.219

Alfa AF: 0.183 Hom.: 452

Bravo AF: 0.258

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.38

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: rs12245255; hg19: chr10-50315080;