1-16053757-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000085.5(CLCNKB):c.1741C>T(p.Leu581Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,610,996 control chromosomes in the GnomAD database, including 333,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29525 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304267 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.515

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 -16 ACMG points.

BP6

Variant 1-16053757-C-T is Benign according to our data. Variant chr1-16053757-C-T is described in ClinVar as Benign. ClinVar VariationId is 447097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.1741C>T	p.Leu581Leu	synonymous_variant	Exon 16 of 20	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0
CLCNKB	NM_001165945.2 link	c.1234C>T	p.Leu412Leu	synonymous_variant	Exon 9 of 13		NP_001159417.2	P51801-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.1741C>T	p.Leu581Leu	synonymous_variant	Exon 16 of 20	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94109

AN:

151610

Hom.:

29518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.618

AC:

154620

AN:

250188

AF XY:

0.618

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.718

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.644

AC:

939123

AN:

1459268

Hom.:

304267

Cov.:

AF XY:

0.640

AC XY:

464968

AN XY:

725956

show subpopulations

African (AFR)

AF:

0.579

AC:

19361

AN:

33464

American (AMR)

AF:

0.496

AC:

22145

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

14708

AN:

26100

East Asian (EAS)

AF:

0.806

AC:

31984

AN:

39690

South Asian (SAS)

AF:

0.532

AC:

45854

AN:

86182

European-Finnish (FIN)

AF:

0.717

AC:

38097

AN:

53116

Middle Eastern (MID)

AF:

0.569

AC:

3274

AN:

5758

European-Non Finnish (NFE)

AF:

0.654

AC:

725360

AN:

1109960

Other (OTH)

AF:

0.636

AC:

38340

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

19066

38132

57198

76264

95330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19014

38028

57042

76056

95070

<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:

0.620

AC:

94135

AN:

151728

Hom.:

29525

Cov.:

AF XY:

0.619

AC XY:

45920

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.585

AC:

24210

AN:

41408

American (AMR)

AF:

0.534

AC:

8144

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1907

AN:

3468

East Asian (EAS)

AF:

0.799

AC:

4119

AN:

5152

South Asian (SAS)

AF:

0.531

AC:

2553

AN:

4806

European-Finnish (FIN)

AF:

0.719

AC:

7556

AN:

10504

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.646

AC:

43787

AN:

67826

Other (OTH)

AF:

0.601

AC:

1267

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1744

3487

5231

6974

8718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.604

Hom.:

7419

Bravo

AF:

0.605

EpiCase

AF:

0.633

EpiControl

AF:

0.627

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 10, 2018

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Leu581Leu in exon 16 of CLCNKB: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 78.99% (6785/8590) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs2275167). -

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

-0.52

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: -8

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