chr18-58316132-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001144967.3(NEDD4L):c.348+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 973,444 control chromosomes in the GnomAD database, including 21,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.24 ( 5346 hom., cov: 32)
Exomes 𝑓: 0.19 ( 16467 hom. )
Consequence
NEDD4L
NM_001144967.3 intron
NM_001144967.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.283
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 18-58316132-A-G is Benign according to our data. Variant chr18-58316132-A-G is described in ClinVar as [Benign]. Clinvar id is 1254207.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEDD4L | NM_001144967.3 | c.348+100A>G | intron_variant | ENST00000400345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEDD4L | ENST00000400345.8 | c.348+100A>G | intron_variant | 1 | NM_001144967.3 | P3 |
Frequencies
GnomAD3 genomes AF: 0.245 AC: 37167AN: 151958Hom.: 5326 Cov.: 32
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GnomAD4 exome AF: 0.192 AC: 157998AN: 821366Hom.: 16467 AF XY: 0.189 AC XY: 80770AN XY: 426488
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GnomAD4 genome AF: 0.245 AC: 37234AN: 152078Hom.: 5346 Cov.: 32 AF XY: 0.240 AC XY: 17815AN XY: 74334
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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 | Jul 06, 2018 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at