Variant rs1912403 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001284338.2(NEDD4):c.97A>G(p.Met33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,614,000 control chromosomes in the GnomAD database, including 6,494 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.066 ( 435 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6059 hom. )

Consequence

NEDD4
NM_001284338.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

NEDD4 (HGNC:7727): (NEDD4 E3 ubiquitin protein ligase) This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

NEDD4 links:

NEDD4 (HGNC:):

NEDD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016183257).

BP6

Variant 15-55916735-T-C is Benign according to our data. Variant chr15-55916735-T-C is described in ClinVar as [Benign]. Clinvar id is 1296895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4 linkuse as main transcript	c.291+7911A>G		intron_variant		ENST00000435532.8	NP_006145.2	P46934-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8 linkuse as main transcript	c.291+7911A>G		intron_variant		1	NM_006154.4	ENSP00000410613.3		P46934-4

Frequencies

GnomAD3 genomes

AF:

0.0663

AC:

10087

AN:

152136

Hom.:

435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.0848

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0484

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0985

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0738

AC:

18557

AN:

251418

Hom.:

892

AF XY:

0.0736

AC XY:

10008

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.0695

Gnomad ASJ exome

AF:

0.0927

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.0476

Gnomad FIN exome

AF:

0.0822

Gnomad NFE exome

AF:

0.0989

Gnomad OTH exome

AF:

0.0735

GnomAD4 exome

AF:

0.0872

AC:

127411

AN:

1461746

Hom.:

6059

Cov.:

AF XY:

0.0863

AC XY:

62734

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.0679

Gnomad4 ASJ exome

AF:

0.0928

Gnomad4 EAS exome

AF:

0.00156

Gnomad4 SAS exome

AF:

0.0479

Gnomad4 FIN exome

AF:

0.0847

Gnomad4 NFE exome

AF:

0.0970

Gnomad4 OTH exome

AF:

0.0776

GnomAD4 genome

AF:

0.0663

AC:

10091

AN:

152254

Hom.:

435

Cov.:

AF XY:

0.0646

AC XY:

4811

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.0709

Gnomad4 ASJ

AF:

0.0848

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0485

Gnomad4 FIN

AF:

0.0809

Gnomad4 NFE

AF:

0.0986

Gnomad4 OTH

AF:

0.0559

Alfa

AF:

0.0875

Hom.:

1603

Bravo

AF:

0.0612

TwinsUK

AF:

0.0976

AC:

362

ALSPAC

AF:

0.0960

AC:

370

ESP6500AA

AF:

0.0164

AC:

ESP6500EA

AF:

0.0907

AC:

778

ExAC

AF:

0.0738

AC:

8965

Asia WGS

AF:

0.0390

AC:

134

AN:

3478

EpiCase

AF:

0.0885

EpiControl

AF:

0.0883

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 30180840) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.089

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.045

D;T;T

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.0040

B;B;B

Vest4

0.12

MPC

0.047

ClinPred

0.0065

GERP RS

4.0

Varity_R

0.085

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over