rs7243360

Variant names:

• chr18-58287559-A-G
• rs7243360
• NM_001144967.3:c.298-28423A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-58287559-A-G
• chr18-58287559-A-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.298-28423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,264 control chromosomes in the GnomAD database, including 65,444 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 0.93 (65444 hom., cov: 32)
• Consequence: NEDD4L NM_001144967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 3 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

ENSG00000303495 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4L	NM_001144967.3	c.298-28423A>G		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.298-28423A>G		intron_variant	Intron 5 of 30	1	NM_001144967.3	ENSP00000383199.2

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141015 AN: 152146 Hom.: 65385 Cov.: 32

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.927 AC: 141135 AN: 152264 Hom.: 65444 Cov.: 32 AF XY: 0.929 AC XY: 69155 AN XY: 74444

African (AFR) AF: 0.949 AC: 39417 AN: 41544

American (AMR) AF: 0.938 AC: 14352 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3120 AN: 3472

East Asian (EAS) AF: 0.957 AC: 4958 AN: 5180

South Asian (SAS) AF: 0.965 AC: 4642 AN: 4812

European-Finnish (FIN) AF: 0.935 AC: 9925 AN: 10610

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61690 AN: 68028

Other (OTH) AF: 0.917 AC: 1938 AN: 2114

Alfa AF: 0.911 Hom.: 206592

Bravo AF: 0.926

Asia WGS AF: 0.971 AC: 3377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.39
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: rs7243360; hg19: chr18-55954791;