dbSNP rs1456099: VEPH1:c.530-30T>A (chr3-157428518-A-T) – 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.530-30T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,600,918 control chromosomes in the GnomAD database, including 192,038 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.44 ( 15869 hom., cov: 32)

Exomes 𝑓: 0.49 ( 176169 hom. )

Consequence

VEPH1
NM_001167912.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2 link	c.530-30T>A		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1	Q14D04-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7 link	c.530-30T>A		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2		Q14D04-1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67536

AN:

151882

Hom.:

15859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.450

GnomAD2 exomes

AF:

0.485

AC:

119351

AN:

246334

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.509

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.489

AC:

709119

AN:

1448916

Hom.:

176169

Cov.:

AF XY:

0.486

AC XY:

350288

AN XY:

720874

show subpopulations

African (AFR)

AF:

0.278

AC:

9254

AN:

33238

American (AMR)

AF:

0.613

AC:

27057

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12346

AN:

25920

East Asian (EAS)

AF:

0.485

AC:

19186

AN:

39598

South Asian (SAS)

AF:

0.362

AC:

31000

AN:

85554

European-Finnish (FIN)

AF:

0.477

AC:

24097

AN:

50526

Middle Eastern (MID)

AF:

0.426

AC:

2445

AN:

5744

European-Non Finnish (NFE)

AF:

0.503

AC:

555582

AN:

1104168

Other (OTH)

AF:

0.469

AC:

28152

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

16603

33206

49810

66413

83016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16062

32124

48186

64248

80310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.445

AC:

67572

AN:

152002

Hom.:

15869

Cov.:

AF XY:

0.445

AC XY:

33036

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.288

AC:

11929

AN:

41474

American (AMR)

AF:

0.578

AC:

8831

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

1660

AN:

3466

East Asian (EAS)

AF:

0.481

AC:

2479

AN:

5152

South Asian (SAS)

AF:

0.372

AC:

1795

AN:

4820

European-Finnish (FIN)

AF:

0.467

AC:

4930

AN:

10546

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.506

AC:

34356

AN:

67958

Other (OTH)

AF:

0.454

AC:

954

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1831

3662

5493

7324

9155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.476

Hom.:

3364

Bravo

AF:

0.447

Asia WGS

AF:

0.445

AC:

1549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

(source)

DANN

Benign

0.60

PhyloP100

0.065

BranchPoint Hunter

2.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over