rs2297727

Positions:

• chr1-16055591-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375679.9(CLCNKB):​c.1845+68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,570,726 control chromosomes in the GnomAD database, including 173,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14487 hom., cov: 31)
  • Exomes 𝑓: 0.47 (158844 hom.)
• Consequence: CLCNKB ENST00000375679.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-16055591-C-T is Benign according to our data. Variant chr1-16055591-C-T is described in ClinVar as [Benign]. Clinvar id is 1229089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5	c.1845+68C>T		intron_variant		ENST00000375679.9	NP_000076.2
CLCNKB	NM_001165945.2	c.1338+68C>T		intron_variant			NP_001159417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9	c.1845+68C>T		intron_variant		1	NM_000085.5	ENSP00000364831	P4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64478 AN: 151508 Hom.: 14479 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.468 AC: 664408 AN: 1419100 Hom.: 158844 Cov.: 25 AF XY: 0.468 AC XY: 331124 AN XY: 707604

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.820

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.425 AC: 64505 AN: 151626 Hom.: 14487 Cov.: 31 AF XY: 0.428 AC XY: 31740 AN XY: 74088

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.435

Alfa AF: 0.440 Hom.: 1921

Bravo AF: 0.413

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.40

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: rs2297727; hg19: chr1-16382086;