rs5257
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000085.5(CLCNKB):āc.324A>Gā(p.Ser108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,613,688 control chromosomes in the GnomAD database, including 520,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.70 ( 40556 hom., cov: 32)
Exomes š: 0.81 ( 480017 hom. )
Consequence
CLCNKB
NM_000085.5 synonymous
NM_000085.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.89
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 -16 ACMG points.
BP6
?
Variant 1-16046629-A-G is Benign according to our data. Variant chr1-16046629-A-G is described in ClinVar as [Benign]. Clinvar id is 447104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16046629-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCNKB | NM_000085.5 | c.324A>G | p.Ser108= | synonymous_variant | 4/20 | ENST00000375679.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCNKB | ENST00000375679.9 | c.324A>G | p.Ser108= | synonymous_variant | 4/20 | 1 | NM_000085.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.703 AC: 106696AN: 151836Hom.: 40534 Cov.: 32
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GnomAD3 exomes AF: 0.812 AC: 204128AN: 251366Hom.: 85128 AF XY: 0.819 AC XY: 111246AN XY: 135872
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GnomAD4 exome AF: 0.806 AC: 1178779AN: 1461734Hom.: 480017 Cov.: 58 AF XY: 0.810 AC XY: 588877AN XY: 727184
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GnomAD4 genome ? AF: 0.702 AC: 106740AN: 151954Hom.: 40556 Cov.: 32 AF XY: 0.709 AC XY: 52631AN XY: 74266
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Ser108Ser in exon 4 of CLCNKB: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 98.98% (8566/8654) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs5257). - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 02, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Bartter disease type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Bartter disease type 4B Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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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
DS_AG_spliceai
Position offset: 13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at