Variant 1-16044404-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000085.5(CLCNKB):c.-7-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,021,462 control chromosomes in the GnomAD database, including 190,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22489 hom., cov: 31)

Exomes 𝑓: 0.61 ( 168018 hom. )

Consequence

CLCNKB
NM_000085.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.23

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-16044404-G-A is Benign according to our data. Variant chr1-16044404-G-A is described in ClinVar as [Benign]. Clinvar id is 1277450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.-7-82G>A		intron_variant		ENST00000375679.9	NP_000076.2	P51801-1A8K8H0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.-7-82G>A		intron_variant		1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

78846

AN:

147694

Hom.:

22476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.577

GnomAD4 exome

AF:

0.614

AC:

536826

AN:

873656

Hom.:

168018

AF XY:

0.618

AC XY:

278801

AN XY:

451276

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.705

Gnomad4 ASJ exome

AF:

0.618

Gnomad4 EAS exome

AF:

0.730

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.617

Gnomad4 OTH exome

AF:

0.601

GnomAD4 genome

AF:

0.534

AC:

78877

AN:

147806

Hom.:

22489

Cov.:

AF XY:

0.537

AC XY:

38679

AN XY:

72068

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.611

Gnomad4 EAS

AF:

0.712

Gnomad4 SAS

AF:

0.672

Gnomad4 FIN

AF:

0.554

Gnomad4 NFE

AF:

0.623

Gnomad4 OTH

AF:

0.579

Alfa

AF:

0.559

Hom.:

3174

Bravo

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over