Genetic Variant VEPH1:c.530-9752T>C (chr3-157438240-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698

Publications

53 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.530-9752T>C		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1	Q14D04-1
PTX3	NM_002852.4 link	c.532+326A>G		intron_variant	Intron 2 of 2	ENST00000295927.4	NP_002843.2	P26022

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7 link	c.530-9752T>C		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2		Q14D04-1
PTX3	ENST00000295927.4 link	c.532+326A>G		intron_variant	Intron 2 of 2	1	NM_002852.4	ENSP00000295927.3		P26022

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89293

AN:

151604

Hom.:

26889

Cov.:

show subpopulations

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.:

AF XY:

0.590

AC XY:

43721

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.703

AC:

29132

AN:

41412

American (AMR)

AF:

0.642

AC:

9794

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1749

AN:

3468

East Asian (EAS)

AF:

0.671

AC:

3424

AN:

5106

South Asian (SAS)

AF:

0.623

AC:

2984

AN:

4786

European-Finnish (FIN)

AF:

0.495

AC:

5196

AN:

10506

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35259

AN:

67882

Other (OTH)

AF:

0.566

AC:

1191

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1745

3491

5236

6982

8727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.70

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over