1-16049824-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000085.5(CLCNKB):c.876T>C(p.Cys292Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,613,546 control chromosomes in the GnomAD database, including 691,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 55003 hom., cov: 30)

Exomes 𝑓: 0.93 ( 636872 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.66

Publications

19 publications found

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]

CLCNKB Gene-Disease associations (from GenCC):

Bartter disease type 3
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Bartter disease type 4B
Inheritance: AR Classification: STRONG Submitted by: G2P
Bartter syndrome type 4
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Gitelman syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CLCNKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-16049824-T-C is Benign according to our data. Variant chr1-16049824-T-C is described in ClinVar as Benign. ClinVar VariationId is 377683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.876T>C	p.Cys292Cys	synonymous_variant	Exon 10 of 20	ENST00000375679.9	NP_000076.2
CLCNKB	NM_001165945.2 link	c.369T>C	p.Cys123Cys	synonymous_variant	Exon 3 of 13		NP_001159417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.876T>C	p.Cys292Cys	synonymous_variant	Exon 10 of 20	1	NM_000085.5	ENSP00000364831.5

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126590

AN:

151652

Hom.:

54977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.924

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.941

Gnomad OTH

AF:

0.857

GnomAD2 exomes

AF:

0.917

AC:

230454

AN:

251368

AF XY:

0.922

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.948

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.923

Gnomad NFE exome

AF:

0.943

Gnomad OTH exome

AF:

0.918

GnomAD4 exome

AF:

0.931

AC:

1361297

AN:

1461776

Hom.:

636872

Cov.:

AF XY:

0.932

AC XY:

677745

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.547

AC:

18305

AN:

33476

American (AMR)

AF:

0.941

AC:

42099

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.886

AC:

23151

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39686

AN:

39700

South Asian (SAS)

AF:

0.926

AC:

79869

AN:

86256

European-Finnish (FIN)

AF:

0.923

AC:

49303

AN:

53420

Middle Eastern (MID)

AF:

0.878

AC:

5067

AN:

5768

European-Non Finnish (NFE)

AF:

0.943

AC:

1048740

AN:

1111914

Other (OTH)

AF:

0.912

AC:

55077

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

5602

11204

16805

22407

28009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21536

43072

64608

86144

107680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.835

AC:

126663

AN:

151770

Hom.:

55003

Cov.:

AF XY:

0.837

AC XY:

62076

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.570

AC:

23513

AN:

41274

American (AMR)

AF:

0.907

AC:

13843

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

3061

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5125

AN:

5128

South Asian (SAS)

AF:

0.937

AC:

4510

AN:

4812

European-Finnish (FIN)

AF:

0.924

AC:

9758

AN:

10566

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.941

AC:

63947

AN:

67938

Other (OTH)

AF:

0.859

AC:

1812

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

834

1667

2501

3334

4168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.887

Hom.:

52138

Bravo

AF:

0.820

Asia WGS

AF:

0.948

AC:

3295

AN:

3478

EpiCase

AF:

0.936

EpiControl

AF:

0.938

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 26, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Jul 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Bartter disease type 3

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bartter disease type 4B

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.016

(source)

DANN

Benign

0.40

PhyloP100

-4.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over