rs520210

Positions:

• chr18-58140841-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144967.3(NEDD4L):​c.49-24947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,132 control chromosomes in the GnomAD database, including 10,745 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 0.36 (10745 hom., cov: 33)
• Consequence: NEDD4L NM_001144967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD4L	NM_001144967.3	c.49-24947G>A		intron_variant		ENST00000400345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD4L	ENST00000400345.8	c.49-24947G>A		intron_variant		1	NM_001144967.3	P3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55359 AN: 152014 Hom.: 10747 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55382 AN: 152132 Hom.: 10745 Cov.: 33 AF XY: 0.358 AC XY: 26620 AN XY: 74376

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.406

Alfa AF: 0.434 Hom.: 19876

Bravo AF: 0.361

Asia WGS AF: 0.405 AC: 1407 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	4.6
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs520210; hg19: chr18-55808073;