chr1-16044182-G-C

Variant names:

• chr1-16044182-G-C
• rs9442195
• NM_000085.5:c.-8+302G>C

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.-8+302G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,758 control chromosomes in the GnomAD database, including 6,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6678 hom., cov: 32)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220
• 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 1-16044182-G-C is Benign according to our data. Variant chr1-16044182-G-C is described in ClinVar as Benign. ClinVar VariationId is 1267183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 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.-8+302G>C		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.-8+302G>C		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.-8+302G>C		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.-8+302G>C		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44536 AN: 151640 Hom.: 6679 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.294 AC: 44568 AN: 151758 Hom.: 6678 Cov.: 32 AF XY: 0.295 AC XY: 21865 AN XY: 74168

African (AFR) AF: 0.274 AC: 11332 AN: 41344

American (AMR) AF: 0.243 AC: 3718 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1561 AN: 5138

South Asian (SAS) AF: 0.286 AC: 1371 AN: 4798

European-Finnish (FIN) AF: 0.380 AC: 4014 AN: 10550

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21068 AN: 67874

Other (OTH) AF: 0.276 AC: 582 AN: 2106

Alfa AF: 0.304 Hom.: 908

Bravo AF: 0.280

Asia WGS AF: 0.322 AC: 1119 AN: 3474

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	12
DANN	Benign	0.79
PhyloP100		-0.22
PromoterAI		0.0075	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: rs9442195; hg19: chr1-16370677;