rs34652156

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.46
Variant links:
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
CLCNKBNM_000085.5 linkuse as main transcriptc.1455G>A p.Ala485Ala synonymous_variant 15/20 ENST00000375679.9 NP_000076.2 P51801-1A8K8H0
CLCNKBNM_001165945.2 linkuse as main transcriptc.948G>A p.Ala316Ala synonymous_variant 8/13 NP_001159417.2 P51801-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLCNKBENST00000375679.9 linkuse as main transcriptc.1455G>A p.Ala485Ala synonymous_variant 15/201 NM_000085.5 ENSP00000364831.5 P51801-1

Frequencies

GnomAD3 genomes
AF:
0.0366
AC:
5564
AN:
152182
Hom.:
145
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0588
Gnomad AMI
AF:
0.123
Gnomad AMR
AF:
0.0215
Gnomad ASJ
AF:
0.0513
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0209
Gnomad FIN
AF:
0.0364
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0287
Gnomad OTH
AF:
0.0306
GnomAD3 exomes
AF:
0.0271
AC:
6794
AN:
250566
Hom.:
135
AF XY:
0.0274
AC XY:
3721
AN XY:
135668
show subpopulations
Gnomad AFR exome
AF:
0.0580
Gnomad AMR exome
AF:
0.0117
Gnomad ASJ exome
AF:
0.0489
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0299
Gnomad FIN exome
AF:
0.0370
Gnomad NFE exome
AF:
0.0274
Gnomad OTH exome
AF:
0.0238
GnomAD4 exome
AF:
0.0285
AC:
41633
AN:
1460916
Hom.:
754
Cov.:
37
AF XY:
0.0285
AC XY:
20697
AN XY:
726768
show subpopulations
Gnomad4 AFR exome
AF:
0.0577
Gnomad4 AMR exome
AF:
0.0129
Gnomad4 ASJ exome
AF:
0.0502
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0283
Gnomad4 FIN exome
AF:
0.0356
Gnomad4 NFE exome
AF:
0.0283
Gnomad4 OTH exome
AF:
0.0282
GnomAD4 genome
AF:
0.0366
AC:
5568
AN:
152300
Hom.:
145
Cov.:
33
AF XY:
0.0375
AC XY:
2796
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0587
Gnomad4 AMR
AF:
0.0213
Gnomad4 ASJ
AF:
0.0513
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0211
Gnomad4 FIN
AF:
0.0364
Gnomad4 NFE
AF:
0.0287
Gnomad4 OTH
AF:
0.0302
Alfa
AF:
0.0339
Hom.:
40
Bravo
AF:
0.0367
Asia WGS
AF:
0.0100
AC:
36
AN:
3478
EpiCase
AF:
0.0293
EpiControl
AF:
0.0280

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 submitterclinical testingAthena DiagnosticsJan 11, 2024- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.16
DANN
Benign
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34652156; hg19: chr1-16378739; COSMIC: COSV65160149; COSMIC: COSV65160149; API