rs2050265

Positions:

• chr1-11819642-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.346+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,136,242 control chromosomes in the GnomAD database, including 15,465 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 0.18 (2660 hom., cov: 33)
  • Exomes 𝑓: 0.16 (12805 hom.)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.346+88A>G		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.280+88A>G		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.418+88A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.346+88A>G		intron_variant		1	NM_001286.5	ENSP00000234488	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27232 AN: 152054 Hom.: 2652 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.159 AC: 156800 AN: 984070 Hom.: 12805 AF XY: 0.160 AC XY: 81021 AN XY: 507008

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0957

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.179 AC: 27273 AN: 152172 Hom.: 2660 Cov.: 33 AF XY: 0.179 AC XY: 13331 AN XY: 74390

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.158

Alfa AF: 0.156 Hom.: 2019

Bravo AF: 0.178

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2050265; hg19: chr1-11879699;