1-16049824-T-C

Position:

chr1-16049824-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000085.5(CLCNKB):c.876T>C(p.Cys292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,613,546 control chromosomes in the GnomAD database, including 691,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 55003 hom., cov: 30)

Exomes 𝑓: 0.93 ( 636872 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.66

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-16049824-T-C is Benign according to our data. Variant chr1-16049824-T-C is described in ClinVar as [Benign]. Clinvar id is 377683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16049824-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.876T>C	p.Cys292=	synonymous_variant	10/20	ENST00000375679.9
CLCNKB	NM_001165945.2 linkuse as main transcript	c.369T>C	p.Cys123=	synonymous_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.876T>C	p.Cys292=	synonymous_variant	10/20	1	NM_000085.5	P4	P51801-1

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126590

AN:

151652

Hom.:

54977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.924

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.941

Gnomad OTH

AF:

0.857

GnomAD3 exomes

AF:

0.917

AC:

230454

AN:

251368

Hom.:

106922

AF XY:

0.922

AC XY:

125220

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.948

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.927

Gnomad FIN exome

AF:

0.923

Gnomad NFE exome

AF:

0.943

Gnomad OTH exome

AF:

0.918

GnomAD4 exome

AF:

0.931

AC:

1361297

AN:

1461776

Hom.:

636872

Cov.:

AF XY:

0.932

AC XY:

677745

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.547

Gnomad4 AMR exome

AF:

0.941

Gnomad4 ASJ exome

AF:

0.886

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.926

Gnomad4 FIN exome

AF:

0.923

Gnomad4 NFE exome

AF:

0.943

Gnomad4 OTH exome

AF:

0.912

GnomAD4 genome

AF:

0.835

AC:

126663

AN:

151770

Hom.:

55003

Cov.:

AF XY:

0.837

AC XY:

62076

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.907

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.937

Gnomad4 FIN

AF:

0.924

Gnomad4 NFE

AF:

0.941

Gnomad4 OTH

AF:

0.859

Alfa

AF:

0.887

Hom.:

38799

Bravo

AF:

0.820

Asia WGS

AF:

0.948

AC:

3295

AN:

3478

EpiCase

AF:

0.936

EpiControl

AF:

0.938

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Bartter disease type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Bartter disease type 4B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.016

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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