rs35480349

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: 1.49

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 504914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16050613-G-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
CLCNKB	NM_000085.5 linkuse as main transcript	c.1053+13G>C		intron_variant		ENST00000375679.9
CLCNKB	NM_001165945.2 linkuse as main transcript	c.546+13G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.1053+13G>C		intron_variant		1	NM_000085.5	P4	P51801-1

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

GnomAD3 exomes

AF:

0.239

AC:

59848

AN:

250624

Hom.:

8422

AF XY:

0.243

AC XY:

32976

AN XY:

135538

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 SAS exome

AF:

0.312

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

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.00620

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.192

AC:

29197

AN:

152176

Hom.:

3664

Cov.:

AF XY:

0.194

AC XY:

14458

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.224

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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) . -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

Dann

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over