1-16024780-A-G

Variant names:

Variant summary

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

The NM_004070.4(CLCNKA):c.247A>G(p.Arg83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,634 control chromosomes in the GnomAD database, including 257,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27334 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230521 hom. )

Consequence

CLCNKA
NM_004070.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.107

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 (MetaRNN=1.8806211E-6).

BP6

Variant 1-16024780-A-G is Benign according to our data. Variant chr1-16024780-A-G is described in ClinVar as [Benign]. Clinvar id is 585697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4 link	c.247A>G	p.Arg83Gly	missense_variant	Exon 4 of 20	ENST00000331433.5	NP_004061.3	P51800-1
CLCNKA	NM_001042704.2 link	c.247A>G	p.Arg83Gly	missense_variant	Exon 4 of 20		NP_001036169.1	P51800-3
CLCNKA	NM_001257139.2 link	c.229+852A>G		intron_variant	Intron 3 of 18		NP_001244068.1	P51800-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5 link	c.247A>G	p.Arg83Gly	missense_variant	Exon 4 of 20	1	NM_004070.4	ENSP00000332771.4		P51800-1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89861

AN:

151908

Hom.:

27307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.551

AC:

138274

AN:

251076

Hom.:

39379

AF XY:

0.553

AC XY:

75081

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.757

Gnomad SAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.559

AC:

816601

AN:

1461608

Hom.:

230521

Cov.:

AF XY:

0.559

AC XY:

406144

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.522

Gnomad4 NFE exome

AF:

0.558

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.592

AC:

89927

AN:

152026

Hom.:

27334

Cov.:

AF XY:

0.584

AC XY:

43408

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.703

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.780

Gnomad4 SAS

AF:

0.571

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.599

Alfa

AF:

0.569

Hom.:

10775

Bravo

AF:

0.591

TwinsUK

AF:

0.564

AC:

2092

ALSPAC

AF:

0.551

AC:

2124

ESP6500AA

AF:

0.696

AC:

3067

ESP6500EA

AF:

0.552

AC:

4748

ExAC

AF:

0.563

AC:

68366

Asia WGS

AF:

0.631

AC:

2195

AN:

3478

EpiCase

AF:

0.553

EpiControl

AF:

0.559

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23850580, 21248228) -

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bartter disease type 4B

Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 16, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.0

DANN

Benign

0.89

DEOGEN2

Benign

0.086

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0000019

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.23

Sift

Benign

0.39

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0

.;B

Vest4

0.095

MPC

0.45

ClinPred

0.0049

GERP RS

0.87

Varity_R

0.061

gMVP

0.33

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