Variant 1-11806394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001286.5(CLCN6):c.87+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,454,100 control chromosomes in the GnomAD database, including 2,228 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 0.043 ( 210 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2018 hom. )

Consequence

CLCN6
NM_001286.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49

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:

MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

MTHFR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CLCN6	NM_001286.5 link	c.87+45G>A	intron_variant	ENST00000346436.11	NP_001277.2	P51797-1
CLCN6	NM_001256959.2 link	c.87+45G>A	intron_variant		NP_001243888.2	P51797-6
CLCN6	NR_046428.2 link	n.159+45G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11 link	c.87+45G>A		intron_variant		1	NM_001286.5	ENSP00000234488.9		P51797-1

Frequencies

GnomAD3 genomes

AF:

0.0435

AC:

6615

AN:

152028

Hom.:

211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0435

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0503

AC:

3575

AN:

71084

Hom.:

142

AF XY:

0.0540

AC XY:

2273

AN XY:

42114

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.0410

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0949

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0517

AC:

67366

AN:

1301956

Hom.:

2018

Cov.:

AF XY:

0.0525

AC XY:

33690

AN XY:

642026

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.0410

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0927

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0435

AC:

6612

AN:

152144

Hom.:

210

Cov.:

AF XY:

0.0431

AC XY:

3206

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.0432

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0433

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.111

AC:

383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over