rs7537765

chr1-11827246-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.840+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,599,422 control chromosomes in the GnomAD database, including 21,136 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 0.17 (2428 hom., cov: 30)
  • Exomes 𝑓: 0.16 (18708 hom.)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN6	NM_001286.5	c.840+25A>G		intron_variant		ENST00000346436.11
CLCN6	NM_001256959.2	c.774+25A>G		intron_variant
CLCN6	NR_046428.2	n.896+25A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN6	ENST00000346436.11	c.840+25A>G		intron_variant		1	NM_001286.5	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26174 AN: 151518 Hom.: 2423 Cov.: 30

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.149 AC: 36772 AN: 246508 Hom.: 3019 AF XY: 0.150 AC XY: 20008 AN XY: 133444

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.0943

Gnomad ASJ exome AF: 0.0942

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.158 AC: 229026 AN: 1447786 Hom.: 18708 Cov.: 31 AF XY: 0.158 AC XY: 113673 AN XY: 718528

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.0982

Gnomad4 ASJ exome AF: 0.0932

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.173 AC: 26210 AN: 151636 Hom.: 2428 Cov.: 30 AF XY: 0.172 AC XY: 12778 AN XY: 74084

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.155

Alfa AF: 0.154 Hom.: 4166

Bravo AF: 0.171

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.4
Dann	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7537765; hg19: chr1-11887303; COSMIC: COSV56738694; COSMIC: COSV56738694;