1-16044378-C-CACACACACACAT

Position:

• chr1-16044378-C-CACACACACACAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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

• Frequency:
  • Genomes: 𝑓 0.019 (40 hom., cov: 0)
  • Exomes 𝑓: 0.051 (849 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Likely 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-CACACACACACAT is Benign according to our data. Variant chr1-16044378-C-CACACACACACAT is described in ClinVar as [Likely_benign]. Clinvar id is 1197677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2942/151014) while in subpopulation NFE AF= 0.0308 (2081/67600). AF 95% confidence interval is 0.0297. There are 40 homozygotes in gnomad4. There are 1340 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR,Digenic gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2940 AN: 150908 Hom.: 40 Cov.: 0

Gnomad AFR AF: 0.00721

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0169

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0508 AC: 29352 AN: 577912 Hom.: 849 AF XY: 0.0523 AC XY: 16027 AN XY: 306574

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0705

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0313

Gnomad4 NFE exome AF: 0.0540

Gnomad4 OTH exome AF: 0.0486

GnomAD4 genome AF: 0.0195 AC: 2942 AN: 151014 Hom.: 40 Cov.: 0 AF XY: 0.0182 AC XY: 1340 AN XY: 73678

Gnomad4 AFR AF: 0.00724

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0172

Alfa AF: 0.00822 Hom.: 246

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 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;