chr1-16044217-T-C

Variant names:

• chr1-16044217-T-C
• rs75909377
• NM_000085.5:c.-7-269T>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.-7-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 139,220 control chromosomes in the GnomAD database, including 1,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1627 hom., cov: 32)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.858
• Publications: 3 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=-0.91).
• BP6: Variant 1-16044217-T-C is Benign according to our data. Variant chr1-16044217-T-C is described in ClinVar as Benign. ClinVar VariationId is 1290356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 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.-7-269T>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.-7-269T>C		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.-7-269T>C		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.-7-269T>C		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 19735 AN: 139114 Hom.: 1622 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0583

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0618

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0980

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.142 AC: 19774 AN: 139220 Hom.: 1627 Cov.: 32 AF XY: 0.138 AC XY: 9328 AN XY: 67402

African (AFR) AF: 0.225 AC: 9050 AN: 40310

American (AMR) AF: 0.0942 AC: 1224 AN: 13000

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 197 AN: 3190

East Asian (EAS) AF: 0.0122 AC: 54 AN: 4416

South Asian (SAS) AF: 0.0360 AC: 134 AN: 3718

European-Finnish (FIN) AF: 0.121 AC: 1157 AN: 9540

Middle Eastern (MID) AF: 0.103 AC: 28 AN: 272

European-Non Finnish (NFE) AF: 0.123 AC: 7634 AN: 62072

Other (OTH) AF: 0.131 AC: 249 AN: 1896

Alfa AF: 0.142 Hom.: 245

Bravo AF: 0.130

Asia WGS AF: 0.0370 AC: 130 AN: 3470

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	-0.91
CADD	Benign	3.2
DANN	Benign	0.63
PhyloP100		-0.86
PromoterAI		0.018	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: rs75909377; hg19: chr1-16370712;