Variant rs5252 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000085.5(CLCNKB):c.1308C>T(p.Ile436=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,096 control chromosomes in the GnomAD database, including 11,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1699 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10078 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.36

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-16051720-C-T is Benign according to our data. Variant chr1-16051720-C-T is described in ClinVar as [Benign]. Clinvar id is 585700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16051720-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5 linkuse as main transcript	c.1308C>T	p.Ile436=	synonymous_variant	14/20	ENST00000375679.9	NP_000076.2
CLCNKB	NM_001165945.2 linkuse as main transcript	c.801C>T	p.Ile267=	synonymous_variant	7/13		NP_001159417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.1308C>T	p.Ile436=	synonymous_variant	14/20	1	NM_000085.5	ENSP00000364831	P4	P51801-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20093

AN:

151888

Hom.:

1683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0442

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0961

AC:

24121

AN:

251022

Hom.:

1539

AF XY:

0.0936

AC XY:

12706

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.0506

Gnomad EAS exome

AF:

0.0106

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.0967

GnomAD4 exome

AF:

0.111

AC:

162677

AN:

1460090

Hom.:

10078

Cov.:

AF XY:

0.109

AC XY:

79090

AN XY:

726456

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0522

Gnomad4 ASJ exome

AF:

0.0531

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.0488

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.133

AC:

20150

AN:

152006

Hom.:

1699

Cov.:

AF XY:

0.128

AC XY:

9546

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.0440

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.113

Hom.:

2041

Bravo

AF:

0.132

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.6

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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