1-16022841-C-T

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.100+122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 665,266 control chromosomes in the GnomAD database, including 5,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1160 hom., cov: 33)
  • Exomes 𝑓: 0.12 (4451 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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 1-16022841-C-T is Benign according to our data. Variant chr1-16022841-C-T is described in ClinVar as [Benign]. Clinvar id is 1287202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCNKA	NM_004070.4	c.100+122C>T		intron_variant		ENST00000331433.5
CLCNKA	NM_001042704.2	c.100+122C>T		intron_variant
CLCNKA	NM_001257139.2	c.100+122C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5	c.100+122C>T		intron_variant		1	NM_004070.4	P4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16355 AN: 152152 Hom.: 1155 Cov.: 33

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.122 AC: 62802 AN: 512996 Hom.: 4451 AF XY: 0.121 AC XY: 31472 AN XY: 260740

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.0612

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.107 AC: 16365 AN: 152270 Hom.: 1160 Cov.: 33 AF XY: 0.114 AC XY: 8459 AN XY: 74454

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.112

Alfa AF: 0.109 Hom.: 128

Bravo AF: 0.105

Asia WGS AF: 0.160 AC: 556 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.1
Dann	Benign	0.29

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: rs61771056; hg19: chr1-16349336;