rs198358

Positions:

• chr1-11844019-T-C

Variant summary

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

The NR_037806.1(NPPA-AS1):​n.1205T>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: NPPA-AS1 NR_037806.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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:):

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 (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPA-AS1	NR_037806.1	n.1205T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN6	ENST00000446542.5	n.507T>C		non_coding_transcript_exon_variant	2/4	1
CLCN6	ENST00000400892.3	c.*1687T>C		3_prime_UTR_variant, NMD_transcript_variant	25/27	3
	ENST00000622391.1			downstream_gene_variant

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

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.291

Alfa AF: 0.248 Hom.: 6536

Bravo AF: 0.319

Asia WGS AF: 0.232 AC: 807 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	1.1
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs198358; hg19: chr1-11904076;