rs34652156
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000085.5(CLCNKB):c.1455G>A(p.Ala485Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,613,216 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.037 ( 145 hom., cov: 33)
Exomes 𝑓: 0.028 ( 754 hom. )
Consequence
CLCNKB
NM_000085.5 synonymous
NM_000085.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.46
Genes affected
CLCNKB (HGNC:2027): (chloride voltage-gated channel Kb) The protein encoded by this gene is a member of the family of voltage-gated chloride channels. Chloride channels have several functions, including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. This gene is expressed predominantly in the kidney and may be important for renal salt reabsorption. Mutations in this gene are associated with autosomal recessive Bartter syndrome type 3 (BS3). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 1-16052244-G-A is Benign according to our data. Variant chr1-16052244-G-A is described in ClinVar as [Benign]. Clinvar id is 585703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16052244-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-4.45 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLCNKB | NM_000085.5 | c.1455G>A | p.Ala485Ala | synonymous_variant | 15/20 | ENST00000375679.9 | NP_000076.2 | |
CLCNKB | NM_001165945.2 | c.948G>A | p.Ala316Ala | synonymous_variant | 8/13 | NP_001159417.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLCNKB | ENST00000375679.9 | c.1455G>A | p.Ala485Ala | synonymous_variant | 15/20 | 1 | NM_000085.5 | ENSP00000364831.5 |
Frequencies
GnomAD3 genomes AF: 0.0366 AC: 5564AN: 152182Hom.: 145 Cov.: 33
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GnomAD3 exomes AF: 0.0271 AC: 6794AN: 250566Hom.: 135 AF XY: 0.0274 AC XY: 3721AN XY: 135668
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GnomAD4 exome AF: 0.0285 AC: 41633AN: 1460916Hom.: 754 Cov.: 37 AF XY: 0.0285 AC XY: 20697AN XY: 726768
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GnomAD4 genome AF: 0.0366 AC: 5568AN: 152300Hom.: 145 Cov.: 33 AF XY: 0.0375 AC XY: 2796AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 11, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at