NM_001167912.2:c.530-13784T>G

Variant names:

• chr3-157442272-A-C
• rs2316706
• NM_001167912.2:c.530-13784T>G

Variant summary

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

The NM_001167912.2(VEPH1):​c.530-13784T>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
• Publications: 5 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=-0.91).
• 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 rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.530-13784T>G		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1
PTX3	NM_002852.4	c.533-94A>C		intron_variant	Intron 2 of 2	ENST00000295927.4	NP_002843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.530-13784T>G		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2
PTX3	ENST00000295927.4	c.533-94A>C		intron_variant	Intron 2 of 2	1	NM_002852.4	ENSP00000295927.3

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

African (AFR) AF: 0.709 AC: 15940 AN: 22492

American (AMR) AF: 0.658 AC: 14008 AN: 21276

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 8628 AN: 17430

East Asian (EAS) AF: 0.688 AC: 22894 AN: 33300

South Asian (SAS) AF: 0.593 AC: 31809 AN: 53626

European-Finnish (FIN) AF: 0.498 AC: 16589 AN: 33328

Middle Eastern (MID) AF: 0.501 AC: 1530 AN: 3054

European-Non Finnish (NFE) AF: 0.515 AC: 398693 AN: 773566

Other (OTH) AF: 0.547 AC: 23977 AN: 43794

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

African (AFR) AF: 0.704 AC: 29174 AN: 41468

American (AMR) AF: 0.643 AC: 9830 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3515 AN: 5174

South Asian (SAS) AF: 0.624 AC: 3013 AN: 4828

European-Finnish (FIN) AF: 0.494 AC: 5205 AN: 10528

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35317 AN: 67948

Other (OTH) AF: 0.566 AC: 1191 AN: 2106

Alfa AF: 0.562 Hom.: 3162

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
PhyloP100		0.045
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: rs2316706; hg19: chr3-157160061; COSMIC: COSV55822230;