1-16040844-G-A

Position:

• chr1-16040844-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682338.1(CLCNKB):​c.-289+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,456 control chromosomes in the GnomAD database, including 11,160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11160 hom., cov: 32)
• Consequence: CLCNKB ENST00000682338.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000682338.1	c.-289+384G>A		intron_variant				ENSP00000507062	P4
CLCNKB	ENST00000683578.1	c.-415+384G>A		intron_variant				ENSP00000507430	A1
CLCNKB	ENST00000684324.1	c.-696+384G>A		intron_variant				ENSP00000507937	P4
CLCNKB	ENST00000684545.1	c.-8+384G>A		intron_variant				ENSP00000506733	P4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57811 AN: 151346 Hom.: 11146 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.382 AC: 57861 AN: 151456 Hom.: 11160 Cov.: 32 AF XY: 0.387 AC XY: 28660 AN XY: 74002

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.403

Alfa AF: 0.0812 Hom.: 66

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9442193; hg19: chr1-16367339;