NM_000085.5:c.171G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000085.5(CLCNKB):c.171G>A(p.Gly57Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,076 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0022 ( 10 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.135

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-16045628-G-A is Benign according to our data. Variant chr1-16045628-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 447095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.135 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.171G>A	p.Gly57Gly	synonymous_variant	Exon 3 of 20	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.171G>A	p.Gly57Gly	synonymous_variant	Exon 3 of 20	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

306

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00317

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00236

AC:

594

AN:

251338

AF XY:

0.00241

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00781

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00215

AC:

3148

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1552

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33476

American (AMR)

AF:

0.000984

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000651

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00829

AC:

443

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00227

AC:

2520

AN:

1111922

Other (OTH)

AF:

0.00189

AC:

114

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

192

384

576

768

960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00201

AC:

306

AN:

152316

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41564

American (AMR)

AF:

0.000850

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00499

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00318

AC:

216

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00201

Hom.:

Bravo

AF:

0.00153

EpiCase

AF:

0.00245

EpiControl

AF:

0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CLCNKB: BP4, BP7 -

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 16, 2023

Athena Diagnostics

Significance:Likely 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

-0.50

CADD

Benign

9.5

(source)

DANN

Benign

0.66

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(source)

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

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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