rs17064520

Variant names:

• chr18-58242398-C-T
• rs17064520
• NM_001144967.3:c.123-3029C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144967.3(NEDD4L):​c.123-3029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,088 control chromosomes in the GnomAD database, including 3,200 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 0.19 (3200 hom., cov: 32)
• Consequence: NEDD4L NM_001144967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4L	NM_001144967.3	c.123-3029C>T		intron_variant	Intron 2 of 30	ENST00000400345.8	NP_001138439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4L	ENST00000400345.8	c.123-3029C>T		intron_variant	Intron 2 of 30	1	NM_001144967.3	ENSP00000383199.2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29559 AN: 151970 Hom.: 3192 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.195 AC: 29597 AN: 152088 Hom.: 3200 Cov.: 32 AF XY: 0.197 AC XY: 14653 AN XY: 74344

African (AFR) AF: 0.222 AC: 9193 AN: 41466

American (AMR) AF: 0.194 AC: 2971 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 855 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2273 AN: 5162

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4814

European-Finnish (FIN) AF: 0.165 AC: 1747 AN: 10588

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10528 AN: 67990

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.175 Hom.: 1450

Bravo AF: 0.198

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17064520; hg19: chr18-55909630;