1-16044378-C-CACACACACACACAT

Position:

• chr1-16044378-C-CACACACACACACAT

Variant summary

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

The NM_000085.5(CLCNKB):​c.-7-108_-7-107insACACACACACACAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2880 hom., cov: 0)
  • Exomes 𝑓: 0.14 (3209 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860

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 1-16044378-C-CACACACACACACAT is Benign according to our data. Variant chr1-16044378-C-CACACACACACACAT is described in ClinVar as [Benign]. Clinvar id is 1269181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5	c.-7-108_-7-107insACACACACACACAT		intron_variant		ENST00000375679.9	NP_000076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-7-108_-7-107insACACACACACACAT		intron_variant		1	NM_000085.5	ENSP00000364831.5

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27111 AN: 150902 Hom.: 2877 Cov.: 0

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.198

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.141 AC: 80768 AN: 571598 Hom.: 3209 AF XY: 0.144 AC XY: 43739 AN XY: 303036

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.00776

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.180 AC: 27120 AN: 151010 Hom.: 2880 Cov.: 0 AF XY: 0.183 AC XY: 13495 AN XY: 73688

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.200

Alfa AF: 0.151 Hom.: 246

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 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146972886; hg19: chr1-16370873;