1-16044296-C-G

Position:

• chr1-16044296-C-G

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.-7-190C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,836 control chromosomes in the GnomAD database, including 1,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1969 hom., cov: 31)
• Consequence: CLCNKB NM_000085.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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=-0.88).
• BP6: Variant 1-16044296-C-G is Benign according to our data. Variant chr1-16044296-C-G is described in ClinVar as [Benign]. Clinvar id is 1231049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5	c.-7-190C>G		intron_variant		ENST00000375679.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9	c.-7-190C>G		intron_variant		1	NM_000085.5	P4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23197 AN: 151718 Hom.: 1969 Cov.: 31

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.153 AC: 23206 AN: 151836 Hom.: 1969 Cov.: 31 AF XY: 0.157 AC XY: 11628 AN XY: 74172

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0723 Hom.: 96

Bravo AF: 0.148

Asia WGS AF: 0.263 AC: 914 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 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.74

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: rs9442225; hg19: chr1-16370791;