dbSNP rs17350396: CLCN6:c.*558A>G (chr1-11840781-A-G) – 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.*558A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 167,990 control chromosomes in the GnomAD database, including 1,630 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 0.12 ( 1460 hom., cov: 32)

Exomes 𝑓: 0.13 ( 170 hom. )

Consequence

CLCN6
NM_001286.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

17 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLCN6	NM_001286.5 link	c.*558A>G	3_prime_UTR_variant	Exon 23 of 23	ENST00000346436.11	NP_001277.2	P51797-1
NPPA-AS1	NR_037806.1 link	n.463A>G	non_coding_transcript_exon_variant	Exon 1 of 4
CLCN6	NR_046428.2 link	n.3224A>G	non_coding_transcript_exon_variant	Exon 23 of 23
CLCN6	NM_001256959.2 link	c.*558A>G	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.*558A>G	3_prime_UTR_variant	Exon 23 of 23	1	NM_001286.5	ENSP00000234488.9	P51797-1
CLCN6	ENST00000312413.10 link	c.*558A>G	3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000308367.7	P51797-6
CLCN6	ENST00000400892.3 link	n.*1252-277A>G	intron_variant	Intron 23 of 26	3		ENSP00000496938.1	A0A3B3IRY0
CLCN6	ENST00000446542.5 link	n.-236A>G	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18739

AN:

152082

Hom.:

1463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.0993

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.0975

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.125

AC:

1981

AN:

15790

Hom.:

170

Cov.:

AF XY:

0.134

AC XY:

1108

AN XY:

8274

show subpopulations

African (AFR)

AF:

0.0224

AC:

AN:

802

American (AMR)

AF:

0.0951

AC:

266

AN:

2798

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

AN:

196

East Asian (EAS)

AF:

0.0846

AC:

123

AN:

1454

South Asian (SAS)

AF:

0.208

AC:

340

AN:

1632

European-Finnish (FIN)

AF:

0.125

AC:

AN:

224

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.137

AC:

1093

AN:

7972

Other (OTH)

AF:

0.120

AC:

AN:

682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.123

AC:

18731

AN:

152200

Hom.:

1460

Cov.:

AF XY:

0.124

AC XY:

9192

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0314

AC:

1305

AN:

41556

American (AMR)

AF:

0.0992

AC:

1516

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

681

AN:

3468

East Asian (EAS)

AF:

0.0975

AC:

505

AN:

5180

South Asian (SAS)

AF:

0.206

AC:

993

AN:

4816

European-Finnish (FIN)

AF:

0.169

AC:

1791

AN:

10588

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11399

AN:

68002

Other (OTH)

AF:

0.141

AC:

297

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

829

1659

2488

3318

4147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.157

Hom.:

3496

Bravo

AF:

0.113

Asia WGS

AF:

0.151

AC:

525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.32

(source)

DANN

Benign

0.36

PhyloP100

-1.2

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

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rs17350396

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