1-11838976-G-A

Position:

• chr1-11838976-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286.5(CLCN6):​c.2529+316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 542,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CLCN6 NM_001286.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09444821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.2529+316G>A		intron_variant		ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.2463+316G>A		intron_variant			NP_001243888.2
CLCN6	NR_046428.2	n.2585+316G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.2529+316G>A		intron_variant		1	NM_001286.5	ENSP00000234488	P1
CLCN6	ENST00000376496.4	c.2845G>A	p.Asp949Asn	missense_variant	22/22	5		ENSP00000365679
CLCN6	ENST00000312413.10	c.2463+316G>A		intron_variant		2		ENSP00000308367
CLCN6	ENST00000400892.3	c.*1022+316G>A		intron_variant, NMD_transcript_variant		3		ENSP00000496938

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000685 AC: 1 AN: 146004 Hom.: 0 AF XY: 0.0000128 AC XY: 1 AN XY: 78344

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000454

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 1 AN: 542982 Hom.: 0 Cov.: 0 AF XY: 0.00000346 AC XY: 1 AN XY: 288996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.68
DANN	Benign	0.94
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.36	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.43	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	0.12	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Vest4		0.034
MutPred		0.13		Gain of MoRF binding (P = 0.0513);
MVP		0.47
ClinPred		0.15	T
GERP RS		-6.3

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: rs1023252; hg19: chr1-11899033;