Genetic Variant VEPH1:p.Arg365Gln (chr3-157381189-C-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.1094G>A(p.Arg365Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,613,790 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.030 ( 230 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 201 hom. )

Consequence

VEPH1
NM_001167912.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.337

Publications

7 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:

LINC00881 (HGNC:48567): (long intergenic non-protein coding RNA 881)

LINC00881 links:

LOC101928236 (HGNC:):

LOC101928236 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0013418794).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2 link	c.1094G>A	p.Arg365Gln	missense_variant	Exon 7 of 14	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7 link	c.1094G>A	p.Arg365Gln	missense_variant	Exon 7 of 14	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4543

AN:

152052

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.00775

AC:

1949

AN:

251372

AF XY:

0.00556

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00314

AC:

4585

AN:

1461620

Hom.:

201

Cov.:

AF XY:

0.00269

AC XY:

1953

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.111

AC:

3701

AN:

33476

American (AMR)

AF:

0.00588

AC:

263

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000186

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00375

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.000147

AC:

164

AN:

1111980

Other (OTH)

AF:

0.00696

AC:

420

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

251

502

754

1005

1256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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:

0.0299

AC:

4543

AN:

152170

Hom.:

230

Cov.:

AF XY:

0.0285

AC XY:

2121

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.104

AC:

4308

AN:

41496

American (AMR)

AF:

0.0102

AC:

156

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000416

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68018

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

203

406

608

811

1014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0107

Hom.:

154

Bravo

AF:

0.0332

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0987

AC:

435

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0100

AC:

1217

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.040

.;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.84

T;.;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.67

N;N;N

PhyloP100

0.34

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.35

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.71

T;T;T

Polyphen

0.028

B;B;B

Vest4

0.17

MPC

0.042

ClinPred

0.0036

GERP RS

0.81

Varity_R

0.019

gMVP

0.27

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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