rs6650118

chr1-16051504-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000085.5(CLCNKB):c.1254C>T(p.Thr418=) 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 1,610,352 control chromosomes in the GnomAD database, including 11,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1679 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10057 hom.)
• Consequence: CLCNKB NM_000085.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.62

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-16051504-C-T is Benign according to our data. Variant chr1-16051504-C-T is described in ClinVar as [Benign]. Clinvar id is 585698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16051504-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.62 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	UniProt
CLCNKB	NM_000085.5	c.1254C>T	p.Thr418=	synonymous_variant	13/20	ENST00000375679.9
CLCNKB	NM_001165945.2	c.747C>T	p.Thr249=	synonymous_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.1254C>T	p.Thr418=	synonymous_variant	13/20	1	NM_000085.5	P4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20088 AN: 152014 Hom.: 1663 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.0961 AC: 24157 AN: 251452 Hom.: 1542 AF XY: 0.0935 AC XY: 12712 AN XY: 135896

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.0507

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.0489

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.111 AC: 161443 AN: 1458220 Hom.: 10057 Cov.: 34 AF XY: 0.108 AC XY: 78524 AN XY: 725614

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.0522

Gnomad4 ASJ exome AF: 0.0531

Gnomad4 EAS exome AF: 0.0137

Gnomad4 SAS exome AF: 0.0488

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.132 AC: 20145 AN: 152132 Hom.: 1679 Cov.: 32 AF XY: 0.128 AC XY: 9550 AN XY: 74370

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0567

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0988 Hom.: 549

Bravo AF: 0.132

Asia WGS AF: 0.0540 AC: 189 AN: 3478

EpiCase AF: 0.108

EpiControl AF: 0.107

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 17, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 25, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.084
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs6650118; hg19: chr1-16377999;