Variant chr18-58316098-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001144967.3(NEDD4L):c.348+66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,288,724 control chromosomes in the GnomAD database, including 149,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20911 hom., cov: 31)

Exomes 𝑓: 0.47 ( 128824 hom. )

Consequence

NEDD4L
NM_001144967.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.642

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-58316098-T-C is Benign according to our data. Variant chr18-58316098-T-C is described in ClinVar as [Benign]. Clinvar id is 1235847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4L	NM_001144967.3 link	c.348+66T>C		intron_variant		ENST00000400345.8	NP_001138439.1	Q96PU5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4L	ENST00000400345.8 link	c.348+66T>C		intron_variant		1	NM_001144967.3	ENSP00000383199.2		Q96PU5-1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78764

AN:

151840

Hom.:

20862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.471

AC:

534914

AN:

1136766

Hom.:

128824

AF XY:

0.467

AC XY:

270574

AN XY:

579124

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.591

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.469

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.519

AC:

78867

AN:

151958

Hom.:

20911

Cov.:

AF XY:

0.516

AC XY:

38362

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.630

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.504

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.492

Hom.:

23554

Bravo

AF:

0.528

Asia WGS

AF:

0.438

AC:

1524

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.56

DANN

Benign

0.34

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over