1-16052230-A-T

Variant names:

Variant summary

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

The NM_000085.5(CLCNKB):c.1441A>T(p.Thr481Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,612,846 control chromosomes in the GnomAD database, including 11,747 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1691 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10056 hom. )

Consequence

CLCNKB
NM_000085.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.954

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=0.0018473566).

BP6

Variant 1-16052230-A-T is Benign according to our data. Variant chr1-16052230-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 585702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16052230-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.1441A>T	p.Thr481Ser	missense_variant	Exon 15 of 20	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0
CLCNKB	NM_001165945.2 link	c.934A>T	p.Thr312Ser	missense_variant	Exon 8 of 13		NP_001159417.2	P51801-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.1441A>T	p.Thr481Ser	missense_variant	Exon 15 of 20	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20103

AN:

152102

Hom.:

1675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0752

Gnomad ASJ

AF:

0.0568

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:

0.0956

AC:

23916

AN:

250126

Hom.:

1518

AF XY:

0.0932

AC XY:

12636

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.0480

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0964

GnomAD4 exome

AF:

0.112

AC:

163065

AN:

1460626

Hom.:

10056

Cov.:

AF XY:

0.109

AC XY:

79213

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0522

Gnomad4 ASJ exome

AF:

0.0533

Gnomad4 EAS exome

AF:

0.0137

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:

0.132

AC:

20160

AN:

152220

Hom.:

1691

Cov.:

AF XY:

0.129

AC XY:

9569

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.0568

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:

0.116

Hom.:

362

Bravo

AF:

0.131

TwinsUK

AF:

0.126

AC:

466

ALSPAC

AF:

0.129

AC:

496

ESP6500AA

AF:

0.211

AC:

928

ESP6500EA

AF:

0.110

AC:

942

ExAC

AF:

0.101

AC:

12272

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Aug 31, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 26, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15148291, 14675050, 19226700) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Dec 17, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Uncertain

0.61

.;D;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.91

.;L;.

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Benign

0.24

Sift

Benign

0.27

.;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.058

.;B;.

Vest4

0.22

MutPred

0.27

.;Loss of helix (P = 0.0196);.;

MPC

0.18

ClinPred

0.031

GERP RS

-3.3

Varity_R

0.16

gMVP

0.43

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