chr1-16040844-G-A

Variant names:

• chr1-16040844-G-A
• rs9442193
• ENST00000682338.1:c.-289+384G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682338.1(CLCNKB):​c.-289+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,456 control chromosomes in the GnomAD database, including 11,160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11160 hom., cov: 32)
• Consequence: CLCNKB ENST00000682338.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 4 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682338.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKB	ENST00000682338.1		c.-289+384G>A		intron	N/A	ENSP00000507062.1
	CLCNKB	ENST00000684324.1		c.-696+384G>A		intron	N/A	ENSP00000507937.1
	CLCNKB	ENST00000684545.1		c.-8+384G>A		intron	N/A	ENSP00000506733.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57811 AN: 151346 Hom.: 11146 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.382 AC: 57861 AN: 151456 Hom.: 11160 Cov.: 32 AF XY: 0.387 AC XY: 28660 AN XY: 74002

African (AFR) AF: 0.264 AC: 10846 AN: 41132

American (AMR) AF: 0.464 AC: 7067 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1544 AN: 5144

South Asian (SAS) AF: 0.513 AC: 2464 AN: 4802

European-Finnish (FIN) AF: 0.437 AC: 4578 AN: 10476

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28449 AN: 67896

Other (OTH) AF: 0.403 AC: 847 AN: 2104

Alfa AF: 0.411 Hom.: 16417

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.70
PhyloP100		-1.7
PromoterAI		0.0094	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9442193; hg19: chr1-16367339;