rs375623456
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001144967.3(NEDD4L):c.2186-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000065 in 1,583,746 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 1 hom. )
Consequence
NEDD4L
NM_001144967.3 splice_polypyrimidine_tract, intron
NM_001144967.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001700
2
Clinical Significance
Conservation
PhyloP100: -2.49
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=-0.82).
BP6
?
Variant 18-58370388-G-A is Benign according to our data. Variant chr18-58370388-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 417002.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEDD4L | NM_001144967.3 | c.2186-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000400345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEDD4L | ENST00000400345.8 | c.2186-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001144967.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000137 AC: 34AN: 249004Hom.: 1 AF XY: 0.000163 AC XY: 22AN XY: 135084
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GnomAD4 exome AF: 0.0000629 AC: 90AN: 1431564Hom.: 1 Cov.: 27 AF XY: 0.0000826 AC XY: 59AN XY: 714292
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74324
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at