Genetic Variant NM_000085.5:c.-7-108_-7-107insAT (chr1-16044378-C-CAT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000085.5(CLCNKB):c.-7-108_-7-107insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 740,164 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

CLCNKB
NM_000085.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKB	NM_000085.5 link	c.-7-108_-7-107insAT		intron_variant	Intron 1 of 19	ENST00000375679.9	NP_000076.2	P51801-1A8K8H0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKB	ENST00000375679.9 link	c.-7-108_-7-107insAT		intron_variant	Intron 1 of 19	1	NM_000085.5	ENSP00000364831.5		P51801-1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

AN:

588978

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

312552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000306

Gnomad4 ASJ exome

AF:

0.000107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000662

Gnomad4 FIN exome

AF:

0.0000762

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.0000970

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151186

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73774

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over