NM_000085.5:c.1756+315C>T

Variant names:

• chr1-16054087-C-T
• rs10803414
• NM_000085.5:c.1756+315C>T

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.1756+315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,804 control chromosomes in the GnomAD database, including 13,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13751 hom., cov: 32)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.730
• Publications: 9 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=-0.81).
• BP6: Variant 1-16054087-C-T is Benign according to our data. Variant chr1-16054087-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295171.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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.1756+315C>T		intron	N/A	NP_000076.2	P51801-1
	CLCNKB	NM_001165945.2		c.1249+315C>T		intron	N/A	NP_001159417.2	P51801-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKB	ENST00000375679.9	TSL:1 MANE Select	c.1756+315C>T		intron	N/A	ENSP00000364831.5	P51801-1
	CLCNKB	ENST00000906263.1		c.1810+315C>T		intron	N/A	ENSP00000576322.1
	CLCNKB	ENST00000906270.1		c.1810+315C>T		intron	N/A	ENSP00000576329.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61840 AN: 151686 Hom.: 13746 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.407 AC: 61848 AN: 151804 Hom.: 13751 Cov.: 32 AF XY: 0.412 AC XY: 30524 AN XY: 74174

African (AFR) AF: 0.237 AC: 9811 AN: 41420

American (AMR) AF: 0.416 AC: 6338 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3468

East Asian (EAS) AF: 0.806 AC: 4166 AN: 5166

South Asian (SAS) AF: 0.441 AC: 2118 AN: 4798

European-Finnish (FIN) AF: 0.491 AC: 5171 AN: 10522

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31631 AN: 67872

Other (OTH) AF: 0.418 AC: 883 AN: 2112

Alfa AF: 0.432 Hom.: 7914

Bravo AF: 0.394

Asia WGS AF: 0.547 AC: 1898 AN: 3478

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	-0.81
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		0.73
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: rs10803414; hg19: chr1-16380582;