Genetic Variant CLCN6:c.*545G>T (chr1-11840768-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286.5(CLCN6):c.*545G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 171,272 control chromosomes in the GnomAD database, including 3,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3745 hom., cov: 33)

Exomes 𝑓: 0.12 ( 171 hom. )

Consequence

CLCN6
NM_001286.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.22

Publications

25 publications found

Variant links:

Genes affected

CLCN6 (HGNC:2024): (chloride voltage-gated channel 6) This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]

CLCN6 links:

NPPA-AS1 (HGNC:37635): (NPPA antisense RNA 1)

NPPA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLCN6	NM_001286.5 link	c.*545G>T	3_prime_UTR_variant	Exon 23 of 23	ENST00000346436.11	NP_001277.2	P51797-1
NPPA-AS1	NR_037806.1 link	n.450G>T	non_coding_transcript_exon_variant	Exon 1 of 4
CLCN6	NR_046428.2 link	n.3211G>T	non_coding_transcript_exon_variant	Exon 23 of 23
CLCN6	NM_001256959.2 link	c.*545G>T	3_prime_UTR_variant	Exon 22 of 22		NP_001243888.2	P51797-6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLCN6	ENST00000346436.11 link	c.*545G>T	3_prime_UTR_variant	Exon 23 of 23	1	NM_001286.5	ENSP00000234488.9	P51797-1
CLCN6	ENST00000312413.10 link	c.*545G>T	3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000308367.7	P51797-6
CLCN6	ENST00000400892.3 link	n.*1252-290G>T	intron_variant	Intron 23 of 26	3		ENSP00000496938.1	A0A3B3IRY0
CLCN6	ENST00000446542.5 link	n.-249G>T	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29013

AN:

151962

Hom.:

3739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0723

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.121

AC:

2331

AN:

19192

Hom.:

171

Cov.:

AF XY:

0.120

AC XY:

1191

AN XY:

9940

show subpopulations

African (AFR)

AF:

0.323

AC:

298

AN:

922

American (AMR)

AF:

0.105

AC:

316

AN:

3012

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

AN:

310

East Asian (EAS)

AF:

0.00828

AC:

AN:

1812

South Asian (SAS)

AF:

0.143

AC:

284

AN:

1982

European-Finnish (FIN)

AF:

0.0719

AC:

AN:

306

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

1243

AN:

9934

Other (OTH)

AF:

0.133

AC:

117

AN:

878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

200

300

400

500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.191

AC:

29044

AN:

152080

Hom.:

3745

Cov.:

AF XY:

0.188

AC XY:

13999

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.363

AC:

15052

AN:

41442

American (AMR)

AF:

0.131

AC:

1997

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3468

East Asian (EAS)

AF:

0.0104

AC:

AN:

5170

South Asian (SAS)

AF:

0.143

AC:

690

AN:

4818

European-Finnish (FIN)

AF:

0.0723

AC:

765

AN:

10588

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9490

AN:

68002

Other (OTH)

AF:

0.190

AC:

401

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1128

2257

3385

4514

5642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.154

Hom.:

3591

Bravo

AF:

0.202

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.62

(source)

DANN

Benign

0.47

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over