rs150723240

Variant names:

• chr1-16045628-G-A
• rs150723240
• NM_000085.5:c.171G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000085.5(CLCNKB):​c.171G>A​(p.Gly57Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,076 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (10 hom.)
• Consequence: CLCNKB NM_000085.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.135
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-16045628-G-A is Benign according to our data. Variant chr1-16045628-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 447095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.171G>A	p.Gly57Gly	synonymous	Exon 3 of 20	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.171G>A	p.Gly57Gly	synonymous	Exon 3 of 20	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.225G>A	p.Gly75Gly	synonymous	Exon 4 of 21	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.225G>A	p.Gly75Gly	synonymous	Exon 4 of 21	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152198 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00236 AC: 594 AN: 251338 AF XY: 0.00241

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00781

Gnomad NFE exome AF: 0.00326

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00215 AC: 3148 AN: 1461760 Hom.: 10 Cov.: 35 AF XY: 0.00213 AC XY: 1552 AN XY: 727172

African (AFR) AF: 0.000269 AC: 9 AN: 33476

American (AMR) AF: 0.000984 AC: 44 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00829 AC: 443 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00227 AC: 2520 AN: 1111922

Other (OTH) AF: 0.00189 AC: 114 AN: 60384

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152316 Hom.: 1 Cov.: 34 AF XY: 0.00219 AC XY: 163 AN XY: 74478

African (AFR) AF: 0.000385 AC: 16 AN: 41564

American (AMR) AF: 0.000850 AC: 13 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00201 Hom.: 1

Bravo AF: 0.00153

EpiCase AF: 0.00245

EpiControl AF: 0.00213

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.5
DANN	Benign	0.66
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150723240; hg19: chr1-16372123;