dbSNP rs1023252: CLCN6:c.2529+316G>A (chr1-11838976-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286.5(CLCN6):c.2529+316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 542,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

CLCN6
NM_001286.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.846

Publications

64 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 Gene-Disease associations (from GenCC):

neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

CLCN6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09444821).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLCN6	NM_001286.5	MANE Select	c.2529+316G>A	intron	N/A	NP_001277.2	P51797-1
CLCN6	NM_001256959.2		c.2463+316G>A	intron	N/A	NP_001243888.2	P51797-6
CLCN6	NR_046428.2		n.2585+316G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLCN6	ENST00000346436.11	TSL:1 MANE Select	c.2529+316G>A		intron	N/A	ENSP00000234488.9	P51797-1
CLCN6	ENST00000376496.4	TSL:5	c.2845G>A	p.Asp949Asn	missense	Exon 22 of 22	ENSP00000365679.3	P51797-5
CLCN6	ENST00000910827.1		c.2589+316G>A		intron	N/A	ENSP00000580886.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000685

AC:

AN:

146004

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

542982

Hom.:

Cov.:

AF XY:

0.00000346

AC XY:

AN XY:

288996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15344

American (AMR)

AF:

0.00

AC:

AN:

33634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19542

East Asian (EAS)

AF:

0.00

AC:

AN:

31486

South Asian (SAS)

AF:

0.0000161

AC:

AN:

62024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4000

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

299846

Other (OTH)

AF:

0.00

AC:

AN:

29670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.68

(source)

DANN

Benign

0.94

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.43

PhyloP100

-0.85

PROVEAN

Benign

0.12

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Vest4

0.034

MutPred

0.13

Gain of MoRF binding (P = 0.0513)

MVP

0.47

ClinPred

0.15

GERP RS

-6.3

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over