Variant chr1-16022585-G-A 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 ENST00000331433.5(CLCNKA):c.-7-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,514,344 control chromosomes in the GnomAD database, including 3,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 334 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3336 hom. )

Consequence

CLCNKA
ENST00000331433.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-16022585-G-A is Benign according to our data. Variant chr1-16022585-G-A is described in ClinVar as [Benign]. Clinvar id is 1179730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CLCNKA	NM_004070.4 linkuse as main transcript	c.-7-28G>A	intron_variant	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2 linkuse as main transcript	c.-7-28G>A	intron_variant		NP_001036169.1
CLCNKA	NM_001257139.2 linkuse as main transcript	c.-7-28G>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.-7-28G>A		intron_variant		1	NM_004070.4	ENSP00000332771	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

9178

AN:

152096

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.0961

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0604

Gnomad OTH

AF:

0.0637

GnomAD3 exomes

AF:

0.0715

AC:

10389

AN:

145232

Hom.:

488

AF XY:

0.0755

AC XY:

5750

AN XY:

76126

show subpopulations

Gnomad AFR exome

AF:

0.0463

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.0537

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0638

GnomAD4 exome

AF:

0.0647

AC:

88105

AN:

1362130

Hom.:

3336

Cov.:

AF XY:

0.0668

AC XY:

44917

AN XY:

672490

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.0770

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.0649

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.0612

Gnomad4 OTH exome

AF:

0.0676

GnomAD4 genome

AF:

0.0603

AC:

9182

AN:

152214

Hom.:

334

Cov.:

AF XY:

0.0606

AC XY:

4513

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.0731

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.0954

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0604

Gnomad4 OTH

AF:

0.0635

Alfa

AF:

0.0581

Hom.:

Bravo

AF:

0.0611

Asia WGS

AF:

0.122

AC:

423

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	clinical testing	GeneDx	Dec 26, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.44

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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