1-16023667-C-T

Position:

• chr1-16023667-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004070.4(CLCNKA):​c.101-133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 997,568 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (108 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (75 hom.)
• Consequence: CLCNKA NM_004070.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73

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 -16 ACMG points.

• BP6: Variant 1-16023667-C-T is Benign according to our data. Variant chr1-16023667-C-T is described in ClinVar as [Benign]. Clinvar id is 1291352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.101-133C>T		intron_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.101-133C>T		intron_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.101-133C>T		intron_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.101-133C>T		intron_variant		1	NM_004070.4	ENSP00000332771	P4

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3282 AN: 152126 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00269 AC: 2270 AN: 845324 Hom.: 75 AF XY: 0.00222 AC XY: 973 AN XY: 437466

Gnomad4 AFR exome AF: 0.0752

Gnomad4 AMR exome AF: 0.00554

Gnomad4 ASJ exome AF: 0.000142

Gnomad4 EAS exome AF: 0.0000617

Gnomad4 SAS exome AF: 0.000160

Gnomad4 FIN exome AF: 0.0000254

Gnomad4 NFE exome AF: 0.000282

Gnomad4 OTH exome AF: 0.00579

GnomAD4 genome AF: 0.0216 AC: 3286 AN: 152244 Hom.: 108 Cov.: 33 AF XY: 0.0203 AC XY: 1514 AN XY: 74426

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0179 Hom.: 7

Bravo AF: 0.0254

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs57147817; hg19: chr1-16350162;