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. The variant received -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
• Publications: 2 publications found

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]

CLCNKB Gene-Disease associations (from GenCC):

• Bartter disease type 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Bartter disease type 4B

  Inheritance: AR Classification: STRONG Submitted by: G2P
• Bartter syndrome type 4

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Gitelman syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 1260229.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKB	NM_000085.5	MANE Select	c.-7-108_-7-107insACACACACAT		intron	N/A	NP_000076.2	P51801-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKB	ENST00000375679.9	TSL:1 MANE Select	c.-7-108_-7-107insACACACACAT		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906274.1		c.-115_-114insACACACACAT		5_prime_UTR	Exon 1 of 19	ENSP00000576333.1
	CLCNKB	ENST00000906263.1		c.-7-108_-7-107insACACACACAT		intron	N/A	ENSP00000576322.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44008 AN: 150852 Hom.: 7257 Cov.: 0

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

African (AFR) AF: 0.0963 AC: 1666 AN: 17298

American (AMR) AF: 0.265 AC: 8302 AN: 31364

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 4422 AN: 18116

East Asian (EAS) AF: 0.437 AC: 12991 AN: 29706

South Asian (SAS) AF: 0.250 AC: 14279 AN: 57214

European-Finnish (FIN) AF: 0.237 AC: 9043 AN: 38164

Middle Eastern (MID) AF: 0.248 AC: 595 AN: 2400

European-Non Finnish (NFE) AF: 0.262 AC: 90180 AN: 343818

Other (OTH) AF: 0.258 AC: 7696 AN: 29830

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

African (AFR) AF: 0.138 AC: 5711 AN: 41288

American (AMR) AF: 0.328 AC: 4963 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1110 AN: 3460

East Asian (EAS) AF: 0.652 AC: 3330 AN: 5108

South Asian (SAS) AF: 0.349 AC: 1650 AN: 4724

European-Finnish (FIN) AF: 0.288 AC: 2995 AN: 10404

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23306 AN: 67558

Other (OTH) AF: 0.308 AC: 641 AN: 2084

Alfa AF: 0.188 Hom.: 246

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146972886; hg19: chr1-16370873; COSMIC: COSV107483953; COSMIC: COSV107483953;