rs1010069

Positions:

• chr1-16026442-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.499-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,551,842 control chromosomes in the GnomAD database, including 177,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20589 hom., cov: 31)
  • Exomes 𝑓: 0.47 (157000 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.754

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=-0.89).
• BP6: Variant 1-16026442-G-A is Benign according to our data. Variant chr1-16026442-G-A is described in ClinVar as [Benign]. Clinvar id is 1278622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKA	NM_004070.4	c.499-94G>A		intron_variant		ENST00000331433.5
CLCNKA	NM_001042704.2	c.499-94G>A		intron_variant
CLCNKA	NM_001257139.2	c.370-94G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5	c.499-94G>A		intron_variant		1	NM_004070.4	P4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77369 AN: 151816 Hom.: 20571 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.469 AC: 656313 AN: 1399908 Hom.: 157000 Cov.: 26 AF XY: 0.470 AC XY: 328191 AN XY: 697724

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.731

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.510 AC: 77417 AN: 151934 Hom.: 20589 Cov.: 31 AF XY: 0.505 AC XY: 37466 AN XY: 74246

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.523

Alfa AF: 0.468 Hom.: 22450

Bravo AF: 0.515

Asia WGS AF: 0.598 AC: 2077 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.70

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: rs1010069; hg19: chr1-16352937; COSMIC: COSV58890920; COSMIC: COSV58890920;