rs58210748

Positions:

• chr1-16029304-GC-G
• chr1-16029304-GC-GCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004070.4(CLCNKA):​c.1227+10del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 152,248 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (20 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLCNKA NM_004070.4 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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 -10 ACMG points.

• BP6: Variant 1-16029304-GC-G is Benign according to our data. Variant chr1-16029304-GC-G is described in ClinVar as [Benign]. Clinvar id is 447083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00669 (1018/152248) while in subpopulation AFR AF= 0.0232 (964/41548). AF 95% confidence interval is 0.022. There are 20 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.1227+10del		splice_donor_region_variant, intron_variant		ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.1227+10del		splice_donor_region_variant, intron_variant			NP_001036169.1
CLCNKA	NM_001257139.2	c.1098+10del		splice_donor_region_variant, intron_variant			NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.1227+10del		splice_donor_region_variant, intron_variant		1	NM_004070.4	ENSP00000332771	P4

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1018 AN: 152130 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00172 AC: 431 AN: 250816 Hom.: 10 AF XY: 0.00130 AC XY: 177 AN XY: 135766

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000654

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000690 AC: 1008 AN: 1461450 Hom.: 7 Cov.: 34 AF XY: 0.000600 AC XY: 436 AN XY: 727032

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000899

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00669 AC: 1018 AN: 152248 Hom.: 20 Cov.: 33 AF XY: 0.00622 AC XY: 463 AN XY: 74440

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000306 Hom.: 0

Bravo AF: 0.00749

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 20, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs58210748; hg19: chr1-16355799;