rs529445

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001144967.3(NEDD4L):​c.49-49523C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,156 control chromosomes in the GnomAD database, including 6,332 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 0.26 ( 6332 hom., cov: 33)

Consequence

NEDD4L
NM_001144967.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEDD4LNM_001144967.3 linkuse as main transcriptc.49-49523C>A intron_variant ENST00000400345.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEDD4LENST00000400345.8 linkuse as main transcriptc.49-49523C>A intron_variant 1 NM_001144967.3 P3Q96PU5-1

Frequencies

GnomAD3 genomes
AF:
0.258
AC:
39278
AN:
152038
Hom.:
6324
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.453
Gnomad AMI
AF:
0.148
Gnomad AMR
AF:
0.197
Gnomad ASJ
AF:
0.261
Gnomad EAS
AF:
0.0835
Gnomad SAS
AF:
0.310
Gnomad FIN
AF:
0.167
Gnomad MID
AF:
0.294
Gnomad NFE
AF:
0.179
Gnomad OTH
AF:
0.248
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.258
AC:
39319
AN:
152156
Hom.:
6332
Cov.:
33
AF XY:
0.257
AC XY:
19122
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.453
Gnomad4 AMR
AF:
0.197
Gnomad4 ASJ
AF:
0.261
Gnomad4 EAS
AF:
0.0831
Gnomad4 SAS
AF:
0.310
Gnomad4 FIN
AF:
0.167
Gnomad4 NFE
AF:
0.179
Gnomad4 OTH
AF:
0.248
Alfa
AF:
0.203
Hom.:
4692
Bravo
AF:
0.267
Asia WGS
AF:
0.193
AC:
672
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.7
DANN
Benign
0.70

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.

Other links and lift over

dbSNP: rs529445; hg19: chr18-55783497; API