1-11806987-T-C

Position:

• chr1-11806987-T-C

Variant summary

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

The NM_001286.5(CLCN6):​c.88-144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 688,060 control chromosomes in the GnomAD database, including 193,869 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 0.75 (42843 hom., cov: 32)
  • Exomes 𝑓: 0.75 (151026 hom.)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.32

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.88-144T>C		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.88-144T>C		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.160-144T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.88-144T>C		intron_variant		1	NM_001286.5	ENSP00000234488.9

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113839 AN: 152000 Hom.: 42792 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.748 AC: 400643 AN: 535942 Hom.: 151026 Cov.: 7 AF XY: 0.741 AC XY: 209997 AN XY: 283464

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.850

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.654

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.749 AC: 113954 AN: 152118 Hom.: 42843 Cov.: 32 AF XY: 0.751 AC XY: 55860 AN XY: 74370

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.726

Alfa AF: 0.740 Hom.: 80154

Bravo AF: 0.751

Asia WGS AF: 0.791 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.44

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: rs3737964; hg19: chr1-11867044;