1-11829411-A-G

Position:

• chr1-11829411-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.1248+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,473,160 control chromosomes in the GnomAD database, including 129,885 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 0.43 (14821 hom., cov: 32)
  • Exomes 𝑓: 0.41 (115064 hom.)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

CLCN6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.1248+89A>G		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.1182+89A>G		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.1304+89A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.1248+89A>G		intron_variant		1	NM_001286.5	ENSP00000234488.9
CLCN6	ENST00000376496.4	c.1248+89A>G		intron_variant		5		ENSP00000365679.3
CLCN6	ENST00000312413.10	c.1182+89A>G		intron_variant		2		ENSP00000308367.7
CLCN6	ENST00000400892.3	n.1248+89A>G		intron_variant		3		ENSP00000496938.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65669 AN: 151964 Hom.: 14808 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.411 AC: 542722 AN: 1321078 Hom.: 115064 AF XY: 0.415 AC XY: 274203 AN XY: 660396

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.432 AC: 65723 AN: 152082 Hom.: 14821 Cov.: 32 AF XY: 0.430 AC XY: 31966 AN XY: 74322

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.430

Alfa AF: 0.406 Hom.: 5476

Bravo AF: 0.429

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.40

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: rs535107; hg19: chr1-11889468; COSMIC: COSV56738838; COSMIC: COSV56738838;