1-11812599-C-T

Position:

• chr1-11812599-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.148-3247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 150,652 control chromosomes in the GnomAD database, including 807 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 0.099 (807 hom., cov: 31)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.148-3247C>T		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.148-4016C>T		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.220-3247C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.148-3247C>T		intron_variant		1	NM_001286.5	ENSP00000234488	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 14930 AN: 150534 Hom.: 810 Cov.: 31

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0826

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

GnomAD4 genome AF: 0.0991 AC: 14926 AN: 150652 Hom.: 807 Cov.: 31 AF XY: 0.0998 AC XY: 7332 AN XY: 73444

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0410 Hom.: 43

Bravo AF: 0.0933

Asia WGS AF: 0.120 AC: 410 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.62

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: rs6687229; hg19: chr1-11872656;