rs1057854

chr1-16057187-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23

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 Likely_benign. Variant got -6 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_single_submitter, 1 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	c.*271G>C		3_prime_UTR_variant	20/20	ENST00000375679.9
CLCNKB	NM_001165945.2	c.*271G>C		3_prime_UTR_variant	13/13

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 46820 AN: 142470 Hom.: 223 Cov.: 41 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.: 0 AF XY: 0.277 AC XY: 69246 AN XY: 250084

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.: 41 AF XY: 0.326 AC XY: 22729 AN XY: 69680

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.: 21

ExAC AF: 0.224 AC: 5374

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
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	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N
Sift4G	Uncertain	0.0090	D
Vest4		0.090
ClinPred		0.0074	T
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

Other links and lift over

dbSNP: rs1057854; hg19: chr1-16383682; COSMIC: COSV65152876; COSMIC: COSV65152876;