1-16023687-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004070.4(CLCNKA):c.101-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,334,422 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (12 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (7 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.658

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=-0.77).
• BP6: Variant 1-16023687-C-T is Benign according to our data. Variant chr1-16023687-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1706874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00517 (787/152310) while in subpopulation AFR AF= 0.0182 (758/41566). AF 95% confidence interval is 0.0172. There are 12 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKA	NM_004070.4	c.101-113C>T		intron_variant		ENST00000331433.5
CLCNKA	NM_001042704.2	c.101-113C>T		intron_variant
CLCNKA	NM_001257139.2	c.101-113C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5	c.101-113C>T		intron_variant		1	NM_004070.4	P4

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 782 AN: 152192 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000486 AC: 575 AN: 1182112 Hom.: 7 AF XY: 0.000419 AC XY: 250 AN XY: 596454

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.000636

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000646

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000228

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00517 AC: 787 AN: 152310 Hom.: 12 Cov.: 33 AF XY: 0.00497 AC XY: 370 AN XY: 74464

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00554

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 08, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	8.8
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs140752147; hg19: chr1-16350182;