Variant chr1-16022959-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004070.4(CLCNKA):c.100+240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,324 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 11 hom., cov: 33)

Consequence

CLCNKA
NM_004070.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-16022959-T-C is Benign according to our data. Variant chr1-16022959-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318226.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0112 (1713/152324) while in subpopulation SAS AF= 0.0363 (175/4818). AF 95% confidence interval is 0.0319. There are 11 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CLCNKA	NM_004070.4 linkuse as main transcript	c.100+240T>C	intron_variant	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2 linkuse as main transcript	c.100+240T>C	intron_variant		NP_001036169.1
CLCNKA	NM_001257139.2 linkuse as main transcript	c.100+240T>C	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.100+240T>C		intron_variant		1	NM_004070.4	ENSP00000332771	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1709

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0359

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0112

AC:

1713

AN:

152324

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

853

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.0100

AC:

AN:

3476

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

GeneDx

Feb 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.47

DANN

Benign

0.64

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