1-16023767-A-G

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.101-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 1,612,362 control chromosomes in the GnomAD database, including 7,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (692 hom., cov: 33)
  • Exomes 𝑓: 0.092 (6756 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589

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=-0.9).
• BP6: Variant 1-16023767-A-G is Benign according to our data. Variant chr1-16023767-A-G is described in ClinVar as [Benign]. Clinvar id is 1222414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKA	NM_004070.4	c.101-33A>G		intron_variant		ENST00000331433.5
CLCNKA	NM_001042704.2	c.101-33A>G		intron_variant
CLCNKA	NM_001257139.2	c.101-33A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5	c.101-33A>G		intron_variant		1	NM_004070.4	P4

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13471 AN: 152118 Hom.: 688 Cov.: 33

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0783

GnomAD3 exomes AF: 0.0760 AC: 19040 AN: 250544 Hom.: 914 AF XY: 0.0754 AC XY: 10225 AN XY: 135562

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0355

Gnomad EAS exome AF: 0.00239

Gnomad SAS exome AF: 0.0442

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.0994

Gnomad OTH exome AF: 0.0798

GnomAD4 exome AF: 0.0918 AC: 134007 AN: 1460126 Hom.: 6756 Cov.: 32 AF XY: 0.0901 AC XY: 65430 AN XY: 726418

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.00696

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0859

GnomAD4 genome AF: 0.0886 AC: 13490 AN: 152236 Hom.: 692 Cov.: 33 AF XY: 0.0859 AC XY: 6398 AN XY: 74442

Gnomad4 AFR AF: 0.0900

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0423

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0770

Alfa AF: 0.0942 Hom.: 164

Bravo AF: 0.0830

Asia WGS AF: 0.0350 AC: 123 AN: 3476

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	-0.90
Cadd	Benign	0.52
Dann	Benign	0.45

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: rs1537803; hg19: chr1-16350262; COSMIC: COSV58894803; COSMIC: COSV58894803;