1-16022585-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004070.4(CLCNKA):c.-7-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,514,344 control chromosomes in the GnomAD database, including 3,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (334 hom., cov: 33)
  • Exomes 𝑓: 0.065 (3336 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

Genes affected

CLCNKA (HGNC:2026): (chloride voltage-gated channel Ka) This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-16022585-G-A is Benign according to our data. Variant chr1-16022585-G-A is described in ClinVar as [Benign]. Clinvar id is 1179730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKA	NM_004070.4	c.-7-28G>A		intron_variant		ENST00000331433.5
CLCNKA	NM_001042704.2	c.-7-28G>A		intron_variant
CLCNKA	NM_001257139.2	c.-7-28G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5	c.-7-28G>A		intron_variant		1	NM_004070.4	P4

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9178 AN: 152096 Hom.: 334 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0637

GnomAD3 exomes AF: 0.0715 AC: 10389 AN: 145232 Hom.: 488 AF XY: 0.0755 AC XY: 5750 AN XY: 76126

Gnomad AFR exome AF: 0.0463

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.0537

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.0267

Gnomad NFE exome AF: 0.0593

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0647 AC: 88105 AN: 1362130 Hom.: 3336 Cov.: 25 AF XY: 0.0668 AC XY: 44917 AN XY: 672490

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.0770

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.0649

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.0676

GnomAD4 genome AF: 0.0603 AC: 9182 AN: 152214 Hom.: 334 Cov.: 33 AF XY: 0.0606 AC XY: 4513 AN XY: 74416

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.0731

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.0954

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0604

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0581 Hom.: 57

Bravo AF: 0.0611

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.44
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs3738637; hg19: chr1-16349080; COSMIC: COSV58891943; COSMIC: COSV58891943;