chr1-11844019-T-C

Variant names:

• chr1-11844019-T-C
• rs198358
• ENST00000446542.5:n.507T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000446542.5(CLCN6):​n.507T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,112 control chromosomes in the GnomAD database, including 8,951 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 0.31 (8951 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLCN6 ENST00000446542.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 67 publications found

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]

NPPA-AS1 (HGNC:37635): (NPPA antisense RNA 1)

ENSG00000276470 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446542.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA-AS1	NR_037806.1		n.1205T>C		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN6	ENST00000446542.5	TSL:1	n.507T>C		non_coding_transcript_exon	Exon 2 of 4
	CLCN6	ENST00000400892.3	TSL:3	n.*1687T>C		non_coding_transcript_exon	Exon 25 of 27	ENSP00000496938.1	A0A3B3IRY0
	CLCN6	ENST00000400892.3	TSL:3	n.*1687T>C		3_prime_UTR	Exon 25 of 27	ENSP00000496938.1	A0A3B3IRY0

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47299 AN: 151994 Hom.: 8936 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.289

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.311 AC: 47355 AN: 152112 Hom.: 8951 Cov.: 32 AF XY: 0.309 AC XY: 22944 AN XY: 74372

African (AFR) AF: 0.532 AC: 22045 AN: 41430

American (AMR) AF: 0.208 AC: 3174 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.143 AC: 742 AN: 5190

South Asian (SAS) AF: 0.303 AC: 1463 AN: 4826

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10592

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16455 AN: 67998

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.256 Hom.: 9023

Bravo AF: 0.319

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs198358; hg19: chr1-11904076;