Variant rs2305619 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

Variant links:

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]

VEPH1 links:

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]

PTX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
VEPH1	NM_001167912.2 linkuse as main transcript	c.530-8584T>C		intron_variant		ENST00000362010.7	NP_001161384.1
PTX3	NM_002852.4 linkuse as main transcript	c.130+9A>G		intron_variant		ENST00000295927.4	NP_002843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4 linkuse as main transcript	c.130+9A>G		intron_variant		1	NM_002852.4	ENSP00000295927	P1
VEPH1	ENST00000362010.7 linkuse as main transcript	c.530-8584T>C		intron_variant		1	NM_001167912.2	ENSP00000354919	P1	Q14D04-1

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77044

AN:

151974

Hom.:

19792

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.546

AC:

137199

AN:

251182

Hom.:

38236

AF XY:

0.547

AC XY:

74324

AN XY:

135774

show subpopulations

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 SAS exome

AF:

0.589

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.:

AF XY:

0.525

AC XY:

381033

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.643

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.585

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.507

AC:

77103

AN:

152092

Hom.:

19800

Cov.:

AF XY:

0.510

AC XY:

37927

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.518

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.511

Hom.:

15176

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

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over