Variant chr18-58044635-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001144967.3(NEDD4L):c.-26C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000628 in 1,593,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

NEDD4L
NM_001144967.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.849

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4L	NM_001144967.3 link	c.-26C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 31	ENST00000400345.8	NP_001138439.1	Q96PU5-1
NEDD4L	NM_001144967.3 link	c.-26C>G		5_prime_UTR_variant	Exon 1 of 31	ENST00000400345.8	NP_001138439.1	Q96PU5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4L	ENST00000400345 link	c.-26C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 31	1	NM_001144967.3	ENSP00000383199.2		Q96PU5-1
NEDD4L	ENST00000400345 link	c.-26C>G		5_prime_UTR_variant	Exon 1 of 31	1	NM_001144967.3	ENSP00000383199.2		Q96PU5-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000453

AC:

AN:

220872

Hom.:

AF XY:

0.00

AC XY:

AN XY:

122372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1441410

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000635

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000382

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.4

DANN

Benign

0.77

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