NM_000085.5:c.-7-108_-7-107insACACACACACACACAT

Variant names:

• chr1-16044378-C-CACACACACACACACAT
• rs146972886
• NM_000085.5:c.-7-108_-7-107insACACACACACACACAT

Variant summary

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

The NM_000085.5(CLCNKB):​c.-7-108_-7-107insACACACACACACACAT 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 0.0053 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0050 (62 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 sas. gnomad4 allele frequency = 0.00534 (807/151174) while in subpopulation SAS AF= 0.0103 (49/4744). AF 95% confidence interval is 0.00803. There are 4 homozygotes in gnomad4. There are 393 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR,Digenic gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 807 AN: 151068 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00449

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.00403

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00916

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00495 AC: 2911 AN: 587948 Hom.: 62 AF XY: 0.00517 AC XY: 1614 AN XY: 312006

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.00602

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.0000967

Gnomad4 SAS exome AF: 0.00780

Gnomad4 FIN exome AF: 0.00310

Gnomad4 NFE exome AF: 0.00525

Gnomad4 OTH exome AF: 0.00463

GnomAD4 genome AF: 0.00534 AC: 807 AN: 151174 Hom.: 4 Cov.: 0 AF XY: 0.00533 AC XY: 393 AN XY: 73768

Gnomad4 AFR AF: 0.00172

Gnomad4 AMR AF: 0.00448

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00403

Gnomad4 NFE AF: 0.00804

Gnomad4 OTH AF: 0.00907

Alfa AF: 0.00186 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;