Variant rs1008899 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000456173.6(NEDD4L):c.-360G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,345,426 control chromosomes in the GnomAD database, including 46,323 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 0.22 ( 4346 hom., cov: 32)

Exomes 𝑓: 0.26 ( 41977 hom. )

Consequence

NEDD4L
ENST00000456173.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.474

Variant links:

Genes affected

NEDD4L (HGNC:7728): (NEDD4 like E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

NEDD4L links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4L	NM_001144967.3 linkuse as main transcript	c.122+29754G>A		intron_variant		ENST00000400345.8
LOC105372143	XR_007066390.1 linkuse as main transcript	n.82C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4L	ENST00000400345.8 linkuse as main transcript	c.122+29754G>A		intron_variant		1	NM_001144967.3	P3	Q96PU5-1
	ENST00000593212.5 linkuse as main transcript	n.62C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33810

AN:

151980

Hom.:

4332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0965

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.283

AC:

62108

AN:

219548

Hom.:

9468

AF XY:

0.284

AC XY:

34313

AN XY:

120778

show subpopulations

Gnomad AFR exome

AF:

0.0939

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.261

AC:

311941

AN:

1193328

Hom.:

41977

Cov.:

AF XY:

0.264

AC XY:

156185

AN XY:

590878

show subpopulations

Gnomad4 AFR exome

AF:

0.0900

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.453

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.222

AC:

33841

AN:

152098

Hom.:

4346

Cov.:

AF XY:

0.223

AC XY:

16578

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0964

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.259

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.261

Hom.:

7329

Bravo

AF:

0.224

Asia WGS

AF:

0.357

AC:

1240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.77

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