rs2236797

chr1-11832593-C-T

Variant summary

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

The NM_001286.5(CLCN6):c.1249-922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 152,262 control chromosomes in the GnomAD database, including 794 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 0.098 (794 hom., cov: 33)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN6	NM_001286.5	c.1249-922C>T		intron_variant		ENST00000346436.11
CLCN6	NM_001256959.2	c.1183-922C>T		intron_variant
CLCN6	NR_046428.2	n.1305-922C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN6	ENST00000346436.11	c.1249-922C>T		intron_variant		1	NM_001286.5	P1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14995 AN: 152144 Hom.: 797 Cov.: 33

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0985 AC: 14992 AN: 152262 Hom.: 794 Cov.: 33 AF XY: 0.0993 AC XY: 7397 AN XY: 74462

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0830

Alfa AF: 0.0986 Hom.: 1468

Bravo AF: 0.0921

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.73
Dann	Benign	0.47

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: rs2236797; hg19: chr1-11892650;