1-16044182-G-C

Position:

• chr1-16044182-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000085.5(CLCNKB):​c.-8+302G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,758 control chromosomes in the GnomAD database, including 6,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6678 hom., cov: 32)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-16044182-G-C is Benign according to our data. Variant chr1-16044182-G-C is described in ClinVar as [Benign]. Clinvar id is 1267183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5	c.-8+302G>C		intron_variant		ENST00000375679.9	NP_000076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-8+302G>C		intron_variant		1	NM_000085.5	ENSP00000364831.5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44536 AN: 151640 Hom.: 6679 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.294 AC: 44568 AN: 151758 Hom.: 6678 Cov.: 32 AF XY: 0.295 AC XY: 21865 AN XY: 74168

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.276

Alfa AF: 0.304 Hom.: 908

Bravo AF: 0.280

Asia WGS AF: 0.322 AC: 1119 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs9442195; hg19: chr1-16370677;