1-16044572-G-T

Position:

chr1-16044572-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000085.5(CLCNKB):c.80G>T(p.Arg27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,600,392 control chromosomes in the GnomAD database, including 316,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R27G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.55 ( 24645 hom., cov: 32)

Exomes 𝑓: 0.63 ( 292311 hom. )

Consequence

CLCNKB
NM_000085.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.00800

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 (MetaRNN=2.8500958E-6).

BP6

Variant 1-16044572-G-T is Benign according to our data. Variant chr1-16044572-G-T is described in ClinVar as [Benign]. Clinvar id is 447107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16044572-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 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.80G>T	p.Arg27Leu	missense_variant	2/20	ENST00000375679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.80G>T	p.Arg27Leu	missense_variant	2/20	1	NM_000085.5	P4	P51801-1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83175

AN:

151712

Hom.:

24634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.627

AC:

142132

AN:

226810

Hom.:

45586

AF XY:

0.632

AC XY:

77223

AN XY:

122216

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.729

Gnomad ASJ exome

AF:

0.683

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.688

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.633

Gnomad OTH exome

AF:

0.633

GnomAD4 exome

AF:

0.632

AC:

915382

AN:

1448564

Hom.:

292311

Cov.:

AF XY:

0.635

AC XY:

456403

AN XY:

719082

show subpopulations

Gnomad4 AFR exome

AF:

0.282

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.679

Gnomad4 EAS exome

AF:

0.690

Gnomad4 SAS exome

AF:

0.685

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.623

GnomAD4 genome

AF:

0.548

AC:

83204

AN:

151828

Hom.:

24645

Cov.:

AF XY:

0.549

AC XY:

40765

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.667

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.558

Gnomad4 NFE

AF:

0.641

Gnomad4 OTH

AF:

0.593

Alfa

AF:

0.600

Hom.:

14996

Bravo

AF:

0.545

TwinsUK

AF:

0.628

AC:

2328

ALSPAC

AF:

0.615

AC:

2372

ESP6500AA

AF:

0.300

AC:

1322

ESP6500EA

AF:

0.642

AC:

5523

ExAC

AF:

0.601

AC:

72401

Asia WGS

AF:

0.613

AC:

2132

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	p.Arg27Leu in exon 2 of CLCNKB: This variant is not expected to have clinical si gnificance because it has been identified in 75.85% (6139/8094) of Latino chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2015352). -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.079

T;T

MetaRNN

Benign

0.0000029

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.88

Sift4G

Uncertain

0.011

D;D

Polyphen

0.47

.;P

Vest4

0.093

MPC

0.046

ClinPred

0.028

GERP RS

3.2

Varity_R

0.14

gMVP

0.58

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