1-16044378-C-CACACAT

Variant names:

• chr1-16044378-C-CACACAT
• rs146972886
• NM_000085.5:c.-7-108_-7-107insACACAT

Variant summary

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

The NM_000085.5(CLCNKB):​c.-7-108_-7-107insACACAT 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 0.022 (67 hom., cov: 0)
  • Exomes 𝑓: 0.026 (627 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 nfe. gnomad4 allele frequency = 0.0223 (3366/151166) while in subpopulation NFE AF= 0.029 (1959/67648). AF 95% confidence interval is 0.0279. There are 67 homozygotes in gnomad4. There are 1678 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 67 AR,Digenic gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3365 AN: 151058 Hom.: 67 Cov.: 0

Gnomad AFR AF: 0.00534

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0673

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0251

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0262 AC: 15333 AN: 585262 Hom.: 627 AF XY: 0.0266 AC XY: 8249 AN XY: 310550

Gnomad4 AFR exome AF: 0.00495

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0579

Gnomad4 EAS exome AF: 0.00713

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0276

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.0223 AC: 3366 AN: 151166 Hom.: 67 Cov.: 0 AF XY: 0.0227 AC XY: 1678 AN XY: 73760

Gnomad4 AFR AF: 0.00535

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0673

Gnomad4 EAS AF: 0.00527

Gnomad4 SAS AF: 0.0221

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0249

Alfa AF: 0.0190 Hom.: 246

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;