rs2316706

chr3-157442272-A-Cchr3-157442272-A-Gchr3-157442272-A-T

Variant summary

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

The NM_001167912.2(VEPH1):c.530-13784T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,153,884 control chromosomes in the GnomAD database, including 171,424 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 0.59 (27035 hom., cov: 33)
  • Exomes 𝑓: 0.53 (144389 hom.)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

Genes affected

VEPH1 (HGNC:25735): (ventricular zone expressed PH domain containing 1) Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PTX3 (HGNC:9692): (pentraxin 3) This gene encodes a member of the pentraxin protein family. The expression of this protein is induced by inflammatory cytokines in response to inflammatory stimuli in several mesenchymal and epithelial cell types, particularly endothelial cells and mononuclear phagocytes. The protein promotes fibrocyte differentiation and is involved in regulating inflammation and complement activation. It also plays a role in angiogenesis and tissue remodeling. The protein serves as a biomarker for several inflammatory conditions. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEPH1	NM_001167912.2	c.530-13784T>G		intron_variant		ENST00000362010.7
PTX3	NM_002852.4	c.533-94A>C		intron_variant		ENST00000295927.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTX3	ENST00000295927.4	c.533-94A>C		intron_variant		1	NM_002852.4	P1
VEPH1	ENST00000362010.7	c.530-13784T>G		intron_variant		1	NM_001167912.2	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89570 AN: 151900 Hom.: 26997 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.533 AC: 534068 AN: 1001866 Hom.: 144389 AF XY: 0.534 AC XY: 266015 AN XY: 498288

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.590 AC: 89676 AN: 152018 Hom.: 27035 Cov.: 33 AF XY: 0.591 AC XY: 43905 AN XY: 74300

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.566

Alfa AF: 0.557 Hom.: 2976

Bravo AF: 0.603

Asia WGS AF: 0.692 AC: 2407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.71

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: rs2316706; hg19: chr3-157160061; COSMIC: COSV55822230;