rs2075539

Positions:

• chr1-11837701-G-A
• chr1-11837701-G-C

Variant summary

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

The NM_001286.5(CLCN6):​c.2295+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 152,270 control chromosomes in the GnomAD database, including 190 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 0.038 (190 hom., cov: 32)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN6	NM_001286.5	c.2295+202G>A		intron_variant		ENST00000346436.11
CLCN6	NM_001256959.2	c.2229+202G>A		intron_variant
CLCN6	NR_046428.2	n.2351+202G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN6	ENST00000346436.11	c.2295+202G>A		intron_variant		1	NM_001286.5	P1
CLCN6	ENST00000312413.10	c.2229+202G>A		intron_variant		2
CLCN6	ENST00000376496.4	c.2295+202G>A		intron_variant		5
CLCN6	ENST00000400892.3	c.*788+202G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5806 AN: 152152 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0381 AC: 5804 AN: 152270 Hom.: 190 Cov.: 32 AF XY: 0.0384 AC XY: 2861 AN XY: 74454

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0428 Hom.: 56

Bravo AF: 0.0370

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	-0.70
CADD	Benign	11
DANN	Benign	0.83

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: rs2075539; hg19: chr1-11897758;