1-11813812-G-T

Variant names:

• chr1-11813812-G-T
• rs12404124
• NM_001286.5:c.148-2034G>T

Variant summary

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

The NM_001286.5(CLCN6):​c.148-2034G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,950 control chromosomes in the GnomAD database, including 24,966 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 0.57 (24966 hom., cov: 33)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.148-2034G>T		intron_variant	Intron 2 of 22	ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.148-2803G>T		intron_variant	Intron 2 of 21		NP_001243888.2
CLCN6	NR_046428.2	n.220-2034G>T		intron_variant	Intron 2 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.148-2034G>T		intron_variant	Intron 2 of 22	1	NM_001286.5	ENSP00000234488.9

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85967 AN: 151832 Hom.: 24949 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.566 AC: 86030 AN: 151950 Hom.: 24966 Cov.: 33 AF XY: 0.568 AC XY: 42195 AN XY: 74278

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.567

Alfa AF: 0.556 Hom.: 10002

Bravo AF: 0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.037
DANN	Benign	0.46

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: rs12404124; hg19: chr1-11873869;