3-157437072-A-G

Variant names:

• chr3-157437072-A-G
• rs2305619
• NM_001167912.2:c.530-8584T>C

Variant summary

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

The NM_001167912.2(VEPH1):​c.530-8584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,612,082 control chromosomes in the GnomAD database, including 221,494 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 0.51 (19800 hom., cov: 33)
  • Exomes 𝑓: 0.52 (201694 hom.)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 93 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.530-8584T>C		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1
PTX3	NM_002852.4	c.130+9A>G		intron_variant	Intron 1 of 2	ENST00000295927.4	NP_002843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.530-8584T>C		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2
PTX3	ENST00000295927.4	c.130+9A>G		intron_variant	Intron 1 of 2	1	NM_002852.4	ENSP00000295927.3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77044 AN: 151974 Hom.: 19792 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.546 AC: 137199 AN: 251182 AF XY: 0.547

Gnomad AFR exome AF: 0.423

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.488

Gnomad EAS exome AF: 0.635

Gnomad FIN exome AF: 0.502

Gnomad NFE exome AF: 0.523

Gnomad OTH exome AF: 0.522

GnomAD4 exome AF: 0.523 AC: 763606 AN: 1459990 Hom.: 201694 Cov.: 41 AF XY: 0.525 AC XY: 381033 AN XY: 726396

African (AFR) AF: 0.415 AC: 13880 AN: 33438

American (AMR) AF: 0.643 AC: 28706 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 12762 AN: 26114

East Asian (EAS) AF: 0.631 AC: 25009 AN: 39658

South Asian (SAS) AF: 0.585 AC: 50352 AN: 86126

European-Finnish (FIN) AF: 0.499 AC: 26614 AN: 53382

Middle Eastern (MID) AF: 0.485 AC: 2796 AN: 5768

European-Non Finnish (NFE) AF: 0.515 AC: 572140 AN: 1110518

Other (OTH) AF: 0.520 AC: 31347 AN: 60312

GnomAD4 genome AF: 0.507 AC: 77103 AN: 152092 Hom.: 19800 Cov.: 33 AF XY: 0.510 AC XY: 37927 AN XY: 74334

African (AFR) AF: 0.423 AC: 17560 AN: 41484

American (AMR) AF: 0.612 AC: 9358 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1736 AN: 3466

East Asian (EAS) AF: 0.637 AC: 3296 AN: 5172

South Asian (SAS) AF: 0.619 AC: 2982 AN: 4814

European-Finnish (FIN) AF: 0.495 AC: 5227 AN: 10568

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35215 AN: 67988

Other (OTH) AF: 0.504 AC: 1062 AN: 2108

Alfa AF: 0.511 Hom.: 18572

Bravo AF: 0.509

Asia WGS AF: 0.646 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		-0.41
PromoterAI		0.031	Neutral
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: rs2305619; hg19: chr3-157154861; COSMIC: COSV55821367; COSMIC: COSV55821367;