rs202013710
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000400345.8(NEDD4L):āc.1980T>Cā(p.Tyr660=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,613,558 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00068 ( 1 hom., cov: 32)
Exomes š: 0.00069 ( 2 hom. )
Consequence
NEDD4L
ENST00000400345.8 synonymous
ENST00000400345.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.150
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 18-58366145-T-C is Benign according to our data. Variant chr18-58366145-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 417014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.15 with no splicing effect.
BS2
High AC in GnomAd4 at 104 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEDD4L | NM_001144967.3 | c.1980T>C | p.Tyr660= | synonymous_variant | 21/31 | ENST00000400345.8 | NP_001138439.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEDD4L | ENST00000400345.8 | c.1980T>C | p.Tyr660= | synonymous_variant | 21/31 | 1 | NM_001144967.3 | ENSP00000383199 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000684 AC: 104AN: 152154Hom.: 1 Cov.: 32
GnomAD3 genomes
AF:
AC:
104
AN:
152154
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000861 AC: 214AN: 248602Hom.: 1 AF XY: 0.000793 AC XY: 107AN XY: 134860
GnomAD3 exomes
AF:
AC:
214
AN:
248602
Hom.:
AF XY:
AC XY:
107
AN XY:
134860
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000693 AC: 1013AN: 1461404Hom.: 2 Cov.: 31 AF XY: 0.000692 AC XY: 503AN XY: 726944
GnomAD4 exome
AF:
AC:
1013
AN:
1461404
Hom.:
Cov.:
31
AF XY:
AC XY:
503
AN XY:
726944
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000684 AC: 104AN: 152154Hom.: 1 Cov.: 32 AF XY: 0.000780 AC XY: 58AN XY: 74332
GnomAD4 genome
AF:
AC:
104
AN:
152154
Hom.:
Cov.:
32
AF XY:
AC XY:
58
AN XY:
74332
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | NEDD4L: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at