Variant rs34652156 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.1455G>A(p.Ala485Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,613,216 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 145 hom., cov: 33)

Exomes 𝑓: 0.028 ( 754 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.46

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:

CLCNKB (HGNC:):

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=-0.82).

BP6

Variant 1-16052244-G-A is Benign according to our data. Variant chr1-16052244-G-A is described in ClinVar as [Benign]. Clinvar id is 585703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16052244-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 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.1455G>A	p.Ala485Ala	synonymous_variant	15/20	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0
CLCNKB	NM_001165945.2 linkuse as main transcript	c.948G>A	p.Ala316Ala	synonymous_variant	8/13		NP_001159417.2	P51801-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.1455G>A	p.Ala485Ala	synonymous_variant	15/20	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5564

AN:

152182

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0271

AC:

6794

AN:

250566

Hom.:

135

AF XY:

0.0274

AC XY:

3721

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.0580

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0489

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0299

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0285

AC:

41633

AN:

1460916

Hom.:

754

Cov.:

AF XY:

0.0285

AC XY:

20697

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0502

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0356

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0366

AC:

5568

AN:

152300

Hom.:

145

Cov.:

AF XY:

0.0375

AC XY:

2796

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0587

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0364

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0302

Alfa

AF:

0.0339

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0280

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 11, 2024	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.16

DANN

Benign

0.48

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