Variant rs1057854 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000085.5(CLCNKB):c.*271G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 224 hom., cov: 41)

Exomes 𝑓: 0.28 ( 114 hom. )

Failed GnomAD Quality Control

Consequence

CLCNKB
NM_000085.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.23

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025365949).

BP6

Variant 1-16057187-G-C is Benign according to our data. Variant chr1-16057187-G-C is described in ClinVar as [Benign]. Clinvar id is 402540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16057187-G-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKB	NM_000085.5 linkuse as main transcript	c.*271G>C		3_prime_UTR_variant	20/20	ENST00000375679.9
CLCNKB	NM_001165945.2 linkuse as main transcript	c.*271G>C		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKB	ENST00000375679.9 linkuse as main transcript	c.*271G>C		3_prime_UTR_variant	20/20	1	NM_000085.5	P4	P51801-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

46820

AN:

142470

Hom.:

223

Cov.:

FAILED QC

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.334

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.275

AC:

126136

AN:

458492

Hom.:

114

Cov.:

AF XY:

0.277

AC XY:

69246

AN XY:

250084

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.249

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.329

AC:

46847

AN:

142580

Hom.:

224

Cov.:

AF XY:

0.326

AC XY:

22729

AN XY:

69680

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.319

Hom.:

ExAC

AF:

0.224

AC:

5374

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.024

DANN

Benign

0.31

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

Sift4G

Uncertain

0.0090

Vest4

0.090

ClinPred

0.0074

GERP RS

-4.9

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

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