Variant 15-55860531-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006154.4(NEDD4):c.836A>G(p.Asn279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,613,736 control chromosomes in the GnomAD database, including 483,395 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.72 ( 40011 hom., cov: 31)

Exomes 𝑓: 0.78 ( 443384 hom. )

Consequence

NEDD4
NM_006154.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.167

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.3675793E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 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.836A>G	p.Asn279Ser	missense_variant	11/29	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.836A>G	p.Asn279Ser	missense_variant	11/29	1	NM_006154.4	ENSP00000410613.3		P46934-4

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109511

AN:

151914

Hom.:

40001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.757

Gnomad FIN

AF:

0.713

Gnomad MID

AF:

0.729

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.698

GnomAD3 exomes

AF:

0.738

AC:

185521

AN:

251344

Hom.:

69214

AF XY:

0.746

AC XY:

101298

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.793

Gnomad EAS exome

AF:

0.585

Gnomad SAS exome

AF:

0.759

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.796

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.777

AC:

1135749

AN:

1461704

Hom.:

443384

Cov.:

AF XY:

0.778

AC XY:

565402

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.604

Gnomad4 AMR exome

AF:

0.665

Gnomad4 ASJ exome

AF:

0.792

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.758

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.799

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.721

AC:

109576

AN:

152032

Hom.:

40011

Cov.:

AF XY:

0.718

AC XY:

53325

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.613

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.802

Gnomad4 EAS

AF:

0.598

Gnomad4 SAS

AF:

0.757

Gnomad4 FIN

AF:

0.713

Gnomad4 NFE

AF:

0.797

Gnomad4 OTH

AF:

0.697

Alfa

AF:

0.776

Hom.:

113448

Bravo

AF:

0.709

TwinsUK

AF:

0.811

AC:

3007

ALSPAC

AF:

0.796

AC:

3067

ESP6500AA

AF:

0.613

AC:

2690

ESP6500EA

AF:

0.795

AC:

6828

ExAC

AF:

0.741

AC:

90007

Asia WGS

AF:

0.671

AC:

2337

AN:

3478

EpiCase

AF:

0.797

EpiControl

AF:

0.781

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.38

DANN

Benign

0.33

DEOGEN2

Benign

0.10

.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.077

T;T;T;T

MetaRNN

Benign

6.4e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.38

.;N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

0.45

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.012

MPC

0.040

ClinPred

0.0085

GERP RS

-7.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.19

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