rs9442225

Variant names:

• chr1-16044296-C-G
• rs9442225
• NM_000085.5:c.-7-190C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-16044296-C-G
• chr1-16044296-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000085.5(CLCNKB):​c.-7-190C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,836 control chromosomes in the GnomAD database, including 1,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.15 (1969 hom., cov: 31)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-16044296-C-G is Benign according to our data. Variant chr1-16044296-C-G is described in ClinVar as Benign. ClinVar VariationId is 1231049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 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.-7-190C>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.-7-190C>G		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.-7-190C>G		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.-7-190C>G		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23197 AN: 151718 Hom.: 1969 Cov.: 31

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.153 AC: 23206 AN: 151836 Hom.: 1969 Cov.: 31 AF XY: 0.157 AC XY: 11628 AN XY: 74172

African (AFR) AF: 0.0941 AC: 3900 AN: 41430

American (AMR) AF: 0.160 AC: 2437 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1455 AN: 5136

South Asian (SAS) AF: 0.199 AC: 958 AN: 4804

European-Finnish (FIN) AF: 0.207 AC: 2183 AN: 10522

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11329 AN: 67916

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.0723 Hom.: 96

Bravo AF: 0.148

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		-1.8
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: rs9442225; hg19: chr1-16370791;