rs3845978

Positions:

• chr3-157441905-C-T

Variant summary

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

The NM_001167912.2(VEPH1):​c.530-13417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 151,886 control chromosomes in the GnomAD database, including 1,108 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 0.094 (1108 hom., cov: 32)
• Consequence: VEPH1 NM_001167912.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEPH1	NM_001167912.2	c.530-13417G>A		intron_variant		ENST00000362010.7
PTX3	NM_002852.4	c.533-461C>T		intron_variant		ENST00000295927.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTX3	ENST00000295927.4	c.533-461C>T		intron_variant		1	NM_002852.4	P1
VEPH1	ENST00000362010.7	c.530-13417G>A		intron_variant		1	NM_001167912.2	P1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14271 AN: 151782 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0752

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

GnomAD4 genome AF: 0.0941 AC: 14292 AN: 151886 Hom.: 1108 Cov.: 32 AF XY: 0.0962 AC XY: 7137 AN XY: 74186

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.0560

Gnomad4 NFE AF: 0.0379

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0507 Hom.: 694

Bravo AF: 0.0951

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.68

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: rs3845978; hg19: chr3-157159694;