1-16053757-C-T

Position:

chr1-16053757-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000085.5(CLCNKB):c.1741C>T(p.Leu581Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,610,996 control chromosomes in the GnomAD database, including 333,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29525 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304267 hom. )

Consequence

CLCNKB
NM_000085.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.515

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-16053757-C-T is Benign according to our data. Variant chr1-16053757-C-T is described in ClinVar as [Benign]. Clinvar id is 447097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16053757-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.1741C>T	p.Leu581Leu	synonymous_variant	16/20	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0
CLCNKB	NM_001165945.2 linkuse as main transcript	c.1234C>T	p.Leu412Leu	synonymous_variant	9/13		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.1741C>T	p.Leu581Leu	synonymous_variant	16/20	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94109

AN:

151610

Hom.:

29518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.618

AC:

154620

AN:

250188

Hom.:

48687

AF XY:

0.618

AC XY:

83662

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.718

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.644

AC:

939123

AN:

1459268

Hom.:

304267

Cov.:

AF XY:

0.640

AC XY:

464968

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.806

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.717

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.620

AC:

94135

AN:

151728

Hom.:

29525

Cov.:

AF XY:

0.619

AC XY:

45920

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.585

Gnomad4 AMR

AF:

0.534

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.601

Alfa

AF:

0.604

Hom.:

7419

Bravo

AF:

0.605

EpiCase

AF:

0.633

EpiControl

AF:

0.627

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

p.Leu581Leu in exon 16 of CLCNKB: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 78.99% (6785/8590) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs2275167). -

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

-0.52

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: -8

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