rs12908466

Variant summary

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

The NM_006154.4(NEDD4):​c.2430+174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,248 control chromosomes in the GnomAD database, including 471 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.

Frequency

Genomes: 𝑓 0.073 ( 471 hom., cov: 32)

Consequence

NEDD4
NM_006154.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.494
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 (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEDD4NM_006154.4 linkuse as main transcriptc.2430+174A>G intron_variant ENST00000435532.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEDD4ENST00000435532.8 linkuse as main transcriptc.2430+174A>G intron_variant 1 NM_006154.4 P1P46934-4

Frequencies

GnomAD3 genomes
AF:
0.0732
AC:
11135
AN:
152130
Hom.:
470
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0370
Gnomad AMI
AF:
0.0835
Gnomad AMR
AF:
0.0793
Gnomad ASJ
AF:
0.0857
Gnomad EAS
AF:
0.00424
Gnomad SAS
AF:
0.0522
Gnomad FIN
AF:
0.0801
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0993
Gnomad OTH
AF:
0.0642
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0732
AC:
11142
AN:
152248
Hom.:
471
Cov.:
32
AF XY:
0.0718
AC XY:
5343
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0370
Gnomad4 AMR
AF:
0.0795
Gnomad4 ASJ
AF:
0.0857
Gnomad4 EAS
AF:
0.00425
Gnomad4 SAS
AF:
0.0520
Gnomad4 FIN
AF:
0.0801
Gnomad4 NFE
AF:
0.0993
Gnomad4 OTH
AF:
0.0636
Alfa
AF:
0.0899
Hom.:
98
Bravo
AF:
0.0696
Asia WGS
AF:
0.0440
AC:
152
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.077
DANN
Benign
0.52

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: rs12908466; hg19: chr15-56126062; API