rs9442224

Variant names:

• chr1-16044246-C-T
• rs9442224
• NM_000085.5:c.-7-240C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000085.5(CLCNKB):​c.-7-240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,788 control chromosomes in the GnomAD database, including 5,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5433 hom., cov: 31)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.404
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-16044246-C-T is Benign according to our data. Variant chr1-16044246-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

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.-7-240C>T		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.-7-240C>T		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.-7-240C>T		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.-7-240C>T		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39623 AN: 151670 Hom.: 5436 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39634 AN: 151788 Hom.: 5433 Cov.: 31 AF XY: 0.262 AC XY: 19409 AN XY: 74160

African (AFR) AF: 0.196 AC: 8118 AN: 41402

American (AMR) AF: 0.228 AC: 3482 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3462

East Asian (EAS) AF: 0.297 AC: 1527 AN: 5142

South Asian (SAS) AF: 0.244 AC: 1174 AN: 4820

European-Finnish (FIN) AF: 0.354 AC: 3732 AN: 10542

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20174 AN: 67850

Other (OTH) AF: 0.247 AC: 522 AN: 2110

Alfa AF: 0.282 Hom.: 783

Bravo AF: 0.248

Asia WGS AF: 0.302 AC: 1051 AN: 3478

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
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.71
PhyloP100		-0.40
PromoterAI		0.0053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9442224; hg19: chr1-16370741;