Variant chr1-16033179-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000331433.5(CLCNKA):c.1939C>T(p.Leu647Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,614,158 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 15 hom. )

Consequence

CLCNKA
ENST00000331433.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.725

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012031764).

BP6

Variant 1-16033179-C-T is Benign according to our data. Variant chr1-16033179-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLCNKA	NM_004070.4 linkuse as main transcript	c.1939C>T	p.Leu647Phe	missense_variant	19/20	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2 linkuse as main transcript	c.1936C>T	p.Leu646Phe	missense_variant	19/20		NP_001036169.1
CLCNKA	NM_001257139.2 linkuse as main transcript	c.1810C>T	p.Leu604Phe	missense_variant	18/19		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.1939C>T	p.Leu647Phe	missense_variant	19/20	1	NM_004070.4	ENSP00000332771	P4	P51800-1
CLCNKA	ENST00000375692.5 linkuse as main transcript	c.1936C>T	p.Leu646Phe	missense_variant	20/21	1		ENSP00000364844	A1	P51800-3
CLCNKA	ENST00000439316.6 linkuse as main transcript	c.1810C>T	p.Leu604Phe	missense_variant	18/19	2		ENSP00000414445		P51800-2
CLCNKA	ENST00000464764.5 linkuse as main transcript	n.2543C>T		non_coding_transcript_exon_variant	23/24	2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

278

AN:

251426

Hom.:

AF XY:

0.00141

AC XY:

192

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00800

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000573

AC:

837

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000788

AC XY:

573

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00774

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000315

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00132

AC:

160

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

3.1

.;.;M

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.3

N;N;N

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.39

MVP

0.87

MPC

0.46

ClinPred

0.086

GERP RS

3.0

Varity_R

0.46

gMVP

0.48

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