Variant rs58150371 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004070.4(CLCNKA):c.1161T>G(p.Leu387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,613,010 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 38 hom. )

Consequence

CLCNKA
NM_004070.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-16029233-T-G is Benign according to our data. Variant chr1-16029233-T-G is described in ClinVar as [Benign]. Clinvar id is 447081.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.038 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1840/152226) while in subpopulation AFR AF= 0.0323 (1341/41538). AF 95% confidence interval is 0.0308. There are 37 homozygotes in gnomad4. There are 850 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLCNKA	NM_004070.4 linkuse as main transcript	c.1161T>G	p.Leu387=	synonymous_variant	12/20	ENST00000331433.5
CLCNKA	NM_001042704.2 linkuse as main transcript	c.1161T>G	p.Leu387=	synonymous_variant	12/20
CLCNKA	NM_001257139.2 linkuse as main transcript	c.1032T>G	p.Leu344=	synonymous_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.1161T>G	p.Leu387=	synonymous_variant	12/20	1	NM_004070.4	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1838

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00464

AC:

1163

AN:

250514

Hom.:

AF XY:

0.00413

AC XY:

560

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.00438

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00487

AC:

7114

AN:

1460784

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3433

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.00450

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.000884

Gnomad4 NFE exome

AF:

0.00490

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.0121

AC:

1840

AN:

152226

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

850

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00477

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.0134

EpiCase

AF:

0.00540

EpiControl

AF:

0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.5

DANN

Benign

0.50

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