dbSNP rs7162435: NEDD4:c.*761A>G (chr15-55829136-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006154.4(NEDD4):c.*761A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,422 control chromosomes in the GnomAD database, including 8,982 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 0.34 ( 8967 hom., cov: 33)

Exomes 𝑓: 0.33 ( 15 hom. )

Consequence

NEDD4
NM_006154.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

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:

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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=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4	NM_006154.4 link	c.*761A>G		3_prime_UTR_variant	Exon 29 of 29	ENST00000435532.8	NP_006145.2	P46934-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532 link	c.*761A>G		3_prime_UTR_variant	Exon 29 of 29	1	NM_006154.4	ENSP00000410613.3		P46934-4

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51626

AN:

151988

Hom.:

8966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.315

GnomAD4 exome

AF:

0.331

AC:

104

AN:

314

Hom.:

Cov.:

AF XY:

0.311

AC XY:

AN XY:

196

show subpopulations

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.340

AC:

51650

AN:

152108

Hom.:

8967

Cov.:

AF XY:

0.341

AC XY:

25333

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.321

Hom.:

8149

Bravo

AF:

0.337

Asia WGS

AF:

0.372

AC:

1296

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.063

DANN

Benign

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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