1-16021917-T-C

Variant names:

• chr1-16021917-T-C
• rs945425
• ENST00000375692.5:c.-82T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375692.5(CLCNKA):​c.-82T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,618 control chromosomes in the GnomAD database, including 38,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37935 hom., cov: 33)
  • Exomes 𝑓: 0.75 (153 hom.)
• Consequence: CLCNKA ENST00000375692.5 splice_region
• Scores: Splicing: ADA: 0.00007013
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.-154T>C		upstream_gene_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.-154T>C		upstream_gene_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.-154T>C		upstream_gene_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.-154T>C		upstream_gene_variant		1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106851 AN: 151972 Hom.: 37913 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.752 AC: 397 AN: 528 Hom.: 153 Cov.: 0 AF XY: 0.751 AC XY: 314 AN XY: 418

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.633

GnomAD4 genome AF: 0.703 AC: 106923 AN: 152090 Hom.: 37935 Cov.: 33 AF XY: 0.702 AC XY: 52214 AN XY: 74340

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.713

Alfa AF: 0.677 Hom.: 54734

Bravo AF: 0.698

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0020

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs945425; hg19: chr1-16348412;