Variant 1-16023833-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004070.4(CLCNKA):c.134G>A(p.Arg45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CLCNKA
NM_004070.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0065775216).

BP6

Variant 1-16023833-G-A is Benign according to our data. Variant chr1-16023833-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 721791.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLCNKA	NM_004070.4 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/20	ENST00000331433.5
CLCNKA	NM_001042704.2 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/20
CLCNKA	NM_001257139.2 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/20	1	NM_004070.4	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00569

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000493

AC:

124

AN:

251416

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152326

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.00111

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:

0.00189

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Benign

0.93

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.029

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.043

.;.;B

Vest4

0.27

MVP

0.79

MPC

0.44

ClinPred

0.015

GERP RS

1.4

Varity_R

0.12

gMVP

0.17

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