18-58044615-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001144967.3(NEDD4L):c.-46C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,563,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
NEDD4L
NM_001144967.3 5_prime_UTR
NM_001144967.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.347
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 18-58044615-C-T is Benign according to our data. Variant chr18-58044615-C-T is described in ClinVar as [Benign]. Clinvar id is 1250867.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEDD4L | NM_001144967.3 | c.-46C>T | 5_prime_UTR_variant | 1/31 | ENST00000400345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEDD4L | ENST00000400345.8 | c.-46C>T | 5_prime_UTR_variant | 1/31 | 1 | NM_001144967.3 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000821 AC: 16AN: 194792Hom.: 0 AF XY: 0.0000368 AC XY: 4AN XY: 108658
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GnomAD4 exome AF: 0.0000120 AC: 17AN: 1410968Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 8AN XY: 699854
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74272
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at