1-16044217-T-C

Position:

• chr1-16044217-T-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.-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

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=-0.91).
• BP6: Variant 1-16044217-T-C is Benign according to our data. Variant chr1-16044217-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5	c.-7-269T>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.-7-269T>C		intron_variant		1	NM_000085.5	ENSP00000364831.5

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

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.0618

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.131

Alfa AF: 0.142 Hom.: 245

Bravo AF: 0.130

Asia WGS AF: 0.0370 AC: 130 AN: 3470

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	-0.91
CADD	Benign	3.2
DANN	Benign	0.63

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: rs75909377; hg19: chr1-16370712;