3-157438240-A-G

Variant names:

• chr3-157438240-A-G
• rs1840680
• NM_001167912.2:c.530-9752T>C

Variant summary

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

The NM_001167912.2(VEPH1):​c.530-9752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,722 control chromosomes in the GnomAD database, including 26,929 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 (26929 hom., cov: 29)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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=-0.85).
• 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.530-9752T>C		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1
PTX3	NM_002852.4	c.532+326A>G		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.530-9752T>C		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2
PTX3	ENST00000295927.4	c.532+326A>G		intron_variant	Intron 2 of 2	1	NM_002852.4	ENSP00000295927.3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89293 AN: 151604 Hom.: 26889 Cov.: 29

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.589 AC: 89401 AN: 151722 Hom.: 26929 Cov.: 29 AF XY: 0.590 AC XY: 43721 AN XY: 74086

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.566

Alfa AF: 0.569 Hom.: 4771

Bravo AF: 0.601

Asia WGS AF: 0.689 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.70

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: rs1840680; hg19: chr3-157156029;