1-16044378-C-CACACACAT

Variant names:

• chr1-16044378-C-CACACACAT
• rs146972886
• NM_000085.5:c.-7-108_-7-107insACACACAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000085.5(CLCNKB):​c.-7-108_-7-107insACACACAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0068 (7 hom., cov: 0)
  • Exomes 𝑓: 0.064 (641 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00675 (1019/150936) while in subpopulation AMR AF= 0.0116 (176/15150). AF 95% confidence interval is 0.0102. There are 7 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5	c.-7-108_-7-107insACACACAT		intron_variant	Intron 1 of 19	ENST00000375679.9	NP_000076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-7-108_-7-107insACACACAT		intron_variant	Intron 1 of 19	1	NM_000085.5	ENSP00000364831.5

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 1020 AN: 150830 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.00652

Gnomad FIN AF: 0.00262

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00898

Gnomad OTH AF: 0.00725

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0639 AC: 36527 AN: 571548 Hom.: 641 AF XY: 0.0633 AC XY: 19210 AN XY: 303266

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0642

Gnomad4 ASJ exome AF: 0.0497

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.0576

Gnomad4 FIN exome AF: 0.0460

Gnomad4 NFE exome AF: 0.0593

Gnomad4 OTH exome AF: 0.0613

GnomAD4 genome AF: 0.00675 AC: 1019 AN: 150936 Hom.: 7 Cov.: 0 AF XY: 0.00634 AC XY: 467 AN XY: 73618

Gnomad4 AFR AF: 0.00240

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00174

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.00654

Gnomad4 FIN AF: 0.00262

Gnomad4 NFE AF: 0.00898

Gnomad4 OTH AF: 0.00718

ClinVar

Not reported in ClinVar

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;