1-16044169-T-G

Variant names:

• chr1-16044169-T-G
• rs2863437
• NM_000085.5:c.-8+289T>G

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+289T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 151,800 control chromosomes in the GnomAD database, including 54,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.83 (54487 hom., cov: 30)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• 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=-0.97).
• BP6: Variant 1-16044169-T-G is Benign according to our data. Variant chr1-16044169-T-G is described in ClinVar as Benign. ClinVar VariationId is 1232074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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+289T>G		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+289T>G		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.-8+289T>G		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.-8+289T>G		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125805 AN: 151682 Hom.: 54464 Cov.: 30

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.829 AC: 125874 AN: 151800 Hom.: 54487 Cov.: 30 AF XY: 0.832 AC XY: 61715 AN XY: 74216

African (AFR) AF: 0.552 AC: 22795 AN: 41268

American (AMR) AF: 0.903 AC: 13798 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5145 AN: 5148

South Asian (SAS) AF: 0.932 AC: 4485 AN: 4812

European-Finnish (FIN) AF: 0.924 AC: 9757 AN: 10564

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63943 AN: 67944

Other (OTH) AF: 0.857 AC: 1809 AN: 2110

Alfa AF: 0.840 Hom.: 3269

Bravo AF: 0.814

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	-0.97
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-2.1
PromoterAI		-0.0098	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: rs2863437; hg19: chr1-16370664;