Variant rs1010069 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004070.4(CLCNKA):c.499-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,551,842 control chromosomes in the GnomAD database, including 177,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20589 hom., cov: 31)

Exomes 𝑓: 0.47 ( 157000 hom. )

Consequence

CLCNKA
NM_004070.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.754

Variant links:

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]

CLCNKA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-16026442-G-A is Benign according to our data. Variant chr1-16026442-G-A is described in ClinVar as [Benign]. Clinvar id is 1278622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CLCNKA	NM_004070.4 linkuse as main transcript	c.499-94G>A	intron_variant	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2 linkuse as main transcript	c.499-94G>A	intron_variant		NP_001036169.1
CLCNKA	NM_001257139.2 linkuse as main transcript	c.370-94G>A	intron_variant		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.499-94G>A		intron_variant		1	NM_004070.4	ENSP00000332771	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77369

AN:

151816

Hom.:

20571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.523

GnomAD4 exome

AF:

0.469

AC:

656313

AN:

1399908

Hom.:

157000

Cov.:

AF XY:

0.470

AC XY:

328191

AN XY:

697724

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.731

Gnomad4 SAS exome

AF:

0.508

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.510

AC:

77417

AN:

151934

Hom.:

20589

Cov.:

AF XY:

0.505

AC XY:

37466

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.776

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.458

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.468

Hom.:

22450

Bravo

AF:

0.515

Asia WGS

AF:

0.598

AC:

2077

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.0

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over