chr13-70139383-ACTGCTG-A

Position:

• chr13-70139383-ACTGCTG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NR_002717.2(ATXN8OS):​n.1143_1148del 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 0.186 in 440,074 control chromosomes in the GnomAD database, including 4,669 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (2441 hom., cov: 0)
  • Exomes 𝑓: 0.18 (2228 hom.)
• Consequence: ATXN8OS NR_002717.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

Genes affected

(HGNC:):

ATXN8OS (HGNC:10561): (ATXN8 opposite strand lncRNA) This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.2	n.1143_1148del		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000673087.1	n.43_48del		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7931_500-7926del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.217 AC: 23473 AN: 108134 Hom.: 2439 Cov.: 0

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.175 AC: 58169 AN: 331902 Hom.: 2228 AF XY: 0.173 AC XY: 30489 AN XY: 175910

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.217 AC: 23482 AN: 108172 Hom.: 2441 Cov.: 0 AF XY: 0.217 AC XY: 11304 AN XY: 52162

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922930; hg19: chr13-70713515;