1-16044404-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000085.5(CLCNKB):c.-7-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,021,462 control chromosomes in the GnomAD database, including 190,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22489 hom., cov: 31)
  • Exomes 𝑓: 0.61 (168018 hom.)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-16044404-G-A is Benign according to our data. Variant chr1-16044404-G-A is described in ClinVar as [Benign]. Clinvar id is 1277450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5	c.-7-82G>A		intron_variant		ENST00000375679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-7-82G>A		intron_variant		1	NM_000085.5	P4

Frequencies

GnomAD3 genomes AF: 0.534 AC: 78846 AN: 147694 Hom.: 22476 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.647

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.614 AC: 536826 AN: 873656 Hom.: 168018 AF XY: 0.618 AC XY: 278801 AN XY: 451276

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.534 AC: 78877 AN: 147806 Hom.: 22489 Cov.: 31 AF XY: 0.537 AC XY: 38679 AN XY: 72068

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.579

Alfa AF: 0.559 Hom.: 3174

Bravo AF: 0.518

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs945394; hg19: chr1-16370899; COSMIC: COSV65160124; COSMIC: COSV65160124;