rs150723240

chr1-16045628-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000085.5(CLCNKB):c.171G>A(p.Gly57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,076 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (10 hom.)
• Consequence: CLCNKB NM_000085.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.135

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-16045628-G-A is Benign according to our data. Variant chr1-16045628-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16045628-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5	c.171G>A	p.Gly57=	synonymous_variant	3/20	ENST00000375679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.171G>A	p.Gly57=	synonymous_variant	3/20	1	NM_000085.5	P4

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152198 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00236 AC: 594 AN: 251338 Hom.: 2 AF XY: 0.00241 AC XY: 327 AN XY: 135884

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00781

Gnomad NFE exome AF: 0.00326

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00215 AC: 3148 AN: 1461760 Hom.: 10 Cov.: 35 AF XY: 0.00213 AC XY: 1552 AN XY: 727172

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00829

Gnomad4 NFE exome AF: 0.00227

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152316 Hom.: 1 Cov.: 34 AF XY: 0.00219 AC XY: 163 AN XY: 74478

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00201 Hom.: 1

Bravo AF: 0.00153

EpiCase AF: 0.00245

EpiControl AF: 0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CLCNKB: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 10, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.5
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs150723240; hg19: chr1-16372123;