15-55860674-C-T

Variant summary

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

The NM_006154.4(NEDD4):​c.779G>A​(p.Arg260Gln) 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 1,613,792 control chromosomes in the GnomAD database, including 483,288 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 ( 40014 hom., cov: 33)
Exomes 𝑓: 0.78 ( 443274 hom. )

Consequence

NEDD4
NM_006154.4 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08
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]

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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=1.0891531E-6).
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
NEDD4NM_006154.4 linkc.779G>A p.Arg260Gln missense_variant 10/29 ENST00000435532.8 NP_006145.2 P46934-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEDD4ENST00000435532.8 linkc.779G>A p.Arg260Gln missense_variant 10/291 NM_006154.4 ENSP00000410613.3 P46934-4

Frequencies

GnomAD3 genomes
AF:
0.721
AC:
109554
AN:
152024
Hom.:
40004
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.612
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:
0.725
Gnomad NFE
AF:
0.797
Gnomad OTH
AF:
0.698
GnomAD3 exomes
AF:
0.738
AC:
185428
AN:
251290
Hom.:
69165
AF XY:
0.746
AC XY:
101244
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.607
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:
0.749
GnomAD4 exome
AF:
0.777
AC:
1135572
AN:
1461650
Hom.:
443274
Cov.:
48
AF XY:
0.777
AC XY:
565326
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.603
Gnomad4 AMR exome
AF:
0.664
Gnomad4 ASJ exome
AF:
0.792
Gnomad4 EAS exome
AF:
0.600
Gnomad4 SAS exome
AF:
0.758
Gnomad4 FIN exome
AF:
0.720
Gnomad4 NFE exome
AF:
0.799
Gnomad4 OTH exome
AF:
0.749
GnomAD4 genome
AF:
0.721
AC:
109619
AN:
152142
Hom.:
40014
Cov.:
33
AF XY:
0.717
AC XY:
53358
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.612
Gnomad4 AMR
AF:
0.688
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:
0.771
Hom.:
95261
Bravo
AF:
0.709
TwinsUK
AF:
0.811
AC:
3007
ALSPAC
AF:
0.796
AC:
3067
ESP6500AA
AF:
0.613
AC:
2690
ESP6500EA
AF:
0.796
AC:
6829
ExAC
AF:
0.741
AC:
89989
Asia WGS
AF:
0.671
AC:
2336
AN:
3478
EpiCase
AF:
0.796
EpiControl
AF:
0.781

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T;.;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.77
T;T;T;T
MetaRNN
Benign
0.0000011
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.0
.;M;.;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.94
N;N;N;N
REVEL
Benign
0.037
Sift
Benign
0.099
T;D;T;D
Sift4G
Benign
0.36
T;T;T;T
Polyphen
0.74
P;P;B;P
Vest4
0.13
MPC
0.060
ClinPred
0.0064
T
GERP RS
2.8
Varity_R
0.076
gMVP
0.35

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.

Other links and lift over

dbSNP: rs2303580; hg19: chr15-56152872; COSMIC: COSV59058686; COSMIC: COSV59058686; API