1-16044378-C-CACACACACAT

Variant names:

• chr1-16044378-C-CACACACACAT
• rs146972886
• NM_000085.5:c.-7-108_-7-107insACACACACAT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

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

• Frequency:
  • Genomes: 𝑓 0.29 (7257 hom., cov: 0)
  • Exomes 𝑓: 0.26 (9773 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-16044378-C-CACACACACAT is Benign according to our data. Variant chr1-16044378-C-CACACACACAT is described in ClinVar as [Benign]. Clinvar id is 1260229.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 44008 AN: 150852 Hom.: 7257 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.308

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.263 AC: 149174 AN: 567910 Hom.: 9773 AF XY: 0.262 AC XY: 78800 AN XY: 301012

Gnomad4 AFR exome AF: 0.0963

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.292 AC: 44005 AN: 150958 Hom.: 7257 Cov.: 0 AF XY: 0.292 AC XY: 21483 AN XY: 73656

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.308

Alfa AF: 0.188 Hom.: 246

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;