1-16044238-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000085.5(CLCNKB):c.-7-247_-7-246del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (24591 hom., cov: 0)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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 -10 ACMG points.

• BP6: Variant 1-16044238-CAG-C is Benign according to our data. Variant chr1-16044238-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1228357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5	c.-7-247_-7-246del		intron_variant		ENST00000375679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-7-247_-7-246del		intron_variant		1	NM_000085.5	P4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82564 AN: 151610 Hom.: 24575 Cov.: 0

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82602 AN: 151728 Hom.: 24591 Cov.: 0 AF XY: 0.547 AC XY: 40551 AN XY: 74150

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.594

Alfa AF: 0.587 Hom.: 3361

Bravo AF: 0.540

Asia WGS AF: 0.633 AC: 2196 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs138811867; hg19: chr1-16370733;