rs1975145

Variant names:

• chr18-58263947-C-T
• rs1975145
• NM_001144967.3:c.297+11893C>T

Variant summary

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

The NM_001144967.3(NEDD4L):​c.297+11893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 150,090 control chromosomes in the GnomAD database, including 2,765 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 0.18 (2765 hom., cov: 32)
• Consequence: NEDD4L NM_001144967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4L	NM_001144967.3	c.297+11893C>T		intron_variant	Intron 5 of 30	ENST00000400345.8	NP_001138439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4L	ENST00000400345.8	c.297+11893C>T		intron_variant	Intron 5 of 30	1	NM_001144967.3	ENSP00000383199.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26757 AN: 149970 Hom.: 2765 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.178 AC: 26758 AN: 150090 Hom.: 2765 Cov.: 32 AF XY: 0.176 AC XY: 12968 AN XY: 73508

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.167

Alfa AF: 0.195 Hom.: 5107

Bravo AF: 0.169

Asia WGS AF: 0.0500 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.22

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: rs1975145; hg19: chr18-55931179;