rs2076001

Positions:

• chr1-11819210-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286.5(CLCN6):​c.280-278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,176 control chromosomes in the GnomAD database, including 801 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 0.099 (801 hom., cov: 33)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.280-278A>G		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.214-278A>G		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.352-278A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.280-278A>G		intron_variant		1	NM_001286.5	ENSP00000234488	P1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15058 AN: 152058 Hom.: 804 Cov.: 33

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0828

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

GnomAD4 genome AF: 0.0989 AC: 15055 AN: 152176 Hom.: 801 Cov.: 33 AF XY: 0.0999 AC XY: 7429 AN XY: 74392

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0938 Hom.: 275

Bravo AF: 0.0928

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.5
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs2076001; hg19: chr1-11879267;