rs2014562

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.492G>C(p.Gly164Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,613,494 control chromosomes in the GnomAD database, including 704,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G164G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.89 ( 60846 hom., cov: 30)

Exomes 𝑓: 0.94 ( 643195 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.502

Publications

20 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: Labcorp Genetics (formerly Invitae), Orphanet
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=-0.59).

BP6

Variant 1-16048038-G-C is Benign according to our data. Variant chr1-16048038-G-C is described in ClinVar as Benign. ClinVar VariationId is 447105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.502 with no splicing effect.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKB	NM_000085.5	MANE Select	c.492G>C	p.Gly164Gly	synonymous	Exon 5 of 20	NP_000076.2	P51801-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLCNKB	ENST00000375679.9	TSL:1 MANE Select	c.492G>C	p.Gly164Gly	synonymous	Exon 5 of 20	ENSP00000364831.5	P51801-1
CLCNKB	ENST00000906263.1		c.546G>C	p.Gly182Gly	synonymous	Exon 6 of 21	ENSP00000576322.1
CLCNKB	ENST00000906270.1		c.546G>C	p.Gly182Gly	synonymous	Exon 6 of 21	ENSP00000576329.1

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135321

AN:

151950

Hom.:

60802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.928

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.938

Gnomad FIN

AF:

0.923

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.942

Gnomad OTH

AF:

0.900

GnomAD2 exomes

AF:

0.932

AC:

233574

AN:

250694

AF XY:

0.933

show subpopulations

Gnomad AFR exome

AF:

0.759

Gnomad AMR exome

AF:

0.958

Gnomad ASJ exome

AF:

0.893

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.923

Gnomad NFE exome

AF:

0.944

Gnomad OTH exome

AF:

0.927

GnomAD4 exome

AF:

0.938

AC:

1370152

AN:

1461426

Hom.:

643195

Cov.:

AF XY:

0.937

AC XY:

681550

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.752

AC:

25179

AN:

33476

American (AMR)

AF:

0.953

AC:

42605

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.886

AC:

23113

AN:

26074

East Asian (EAS)

AF:

1.00

AC:

39678

AN:

39692

South Asian (SAS)

AF:

0.927

AC:

79914

AN:

86226

European-Finnish (FIN)

AF:

0.923

AC:

49273

AN:

53374

Middle Eastern (MID)

AF:

0.887

AC:

5118

AN:

5768

European-Non Finnish (NFE)

AF:

0.944

AC:

1049425

AN:

1111746

Other (OTH)

AF:

0.925

AC:

55847

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

4663

9326

13989

18652

23315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21582

43164

64746

86328

107910

<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:

0.891

AC:

135422

AN:

152068

Hom.:

60846

Cov.:

AF XY:

0.892

AC XY:

66294

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.764

AC:

31616

AN:

41396

American (AMR)

AF:

0.928

AC:

14199

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

3061

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5154

AN:

5156

South Asian (SAS)

AF:

0.939

AC:

4521

AN:

4816

European-Finnish (FIN)

AF:

0.923

AC:

9788

AN:

10600

Middle Eastern (MID)

AF:

0.905

AC:

266

AN:

294

European-Non Finnish (NFE)

AF:

0.942

AC:

64085

AN:

68014

Other (OTH)

AF:

0.901

AC:

1901

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

699

1398

2098

2797

3496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.925

Hom.:

21126

Bravo

AF:

0.884

Asia WGS

AF:

0.960

AC:

3337

AN:

3478

EpiCase

AF:

0.937

EpiControl

AF:

0.939

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Bartter disease type 3 (1)

Bartter disease type 4B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over