rs35480349

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000085.5(CLCNKB):c.1053+13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,612,578 control chromosomes in the GnomAD database, including 46,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3664 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42843 hom. )

Consequence

CLCNKB
NM_000085.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-16050613-G-C is Benign according to our data. Variant chr1-16050613-G-C is described in ClinVar as Benign. ClinVar VariationId is 504914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.1053+13G>C		intron_variant	Intron 11 of 19	ENST00000375679.9	NP_000076.2
CLCNKB	NM_001165945.2 link	c.546+13G>C		intron_variant	Intron 4 of 12		NP_001159417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.1053+13G>C		intron_variant	Intron 11 of 19	1	NM_000085.5	ENSP00000364831.5

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29175

AN:

152058

Hom.:

3653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.239

AC:

59848

AN:

250624

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.234

AC:

342230

AN:

1460402

Hom.:

42843

Cov.:

AF XY:

0.238

AC XY:

172649

AN XY:

726578

show subpopulations

African (AFR)

AF:

0.0395

AC:

1321

AN:

33458

American (AMR)

AF:

0.347

AC:

15531

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

7438

AN:

26108

East Asian (EAS)

AF:

0.00620

AC:

246

AN:

39700

South Asian (SAS)

AF:

0.309

AC:

26682

AN:

86224

European-Finnish (FIN)

AF:

0.210

AC:

11165

AN:

53112

Middle Eastern (MID)

AF:

0.299

AC:

1722

AN:

5766

European-Non Finnish (NFE)

AF:

0.238

AC:

264416

AN:

1110984

Other (OTH)

AF:

0.227

AC:

13709

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

13211

26422

39632

52843

66054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8818

17636

26454

35272

44090

<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:

0.192

AC:

29197

AN:

152176

Hom.:

3664

Cov.:

AF XY:

0.194

AC XY:

14458

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0464

AC:

1930

AN:

41552

American (AMR)

AF:

0.296

AC:

4519

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

990

AN:

3464

East Asian (EAS)

AF:

0.0104

AC:

AN:

5180

South Asian (SAS)

AF:

0.306

AC:

1478

AN:

4826

European-Finnish (FIN)

AF:

0.227

AC:

2412

AN:

10604

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16888

AN:

67960

Other (OTH)

AF:

0.224

AC:

472

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1131

2263

3394

4526

5657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.183

Hom.:

624

Bravo

AF:

0.190

Asia WGS

AF:

0.163

AC:

569

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1053+13G>C in intron 11 of CLCNKB: This variant is not expected to have clinic al significance because it is not located within the splice consensus sequence a nd has been identified in 37.07% (4277/11538) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35480349) .

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

Nov 11, 2018

GeneDx

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.38

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(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

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