rs10803414

Positions:

• chr1-16054087-C-T

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.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

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=-0.81).
• BP6: Variant 1-16054087-C-T is Benign according to our data. Variant chr1-16054087-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5	c.1756+315C>T		intron_variant		ENST00000375679.9
CLCNKB	NM_001165945.2	c.1249+315C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.1756+315C>T		intron_variant		1	NM_000085.5	P4

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.418

Alfa AF: 0.434 Hom.: 6820

Bravo AF: 0.394

Asia WGS AF: 0.547 AC: 1898 AN: 3478

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	-0.81
CADD	Benign	6.3
DANN	Benign	0.54

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: rs10803414; hg19: chr1-16380582;