13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NR_002717.2(ATXN8OS):​n.1131_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 0.00848 in 457,394 control chromosomes in the GnomAD database, including 43 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 0)
  • Exomes 𝑓: 0.0077 (26 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 1204 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN8OS	NR_002717.2	n.1131_1148del		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000673087.1	n.31_48del		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7943_500-7926del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1205 AN: 109084 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00411

Gnomad ASJ AF: 0.00702

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.00442

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00355

GnomAD4 exome AF: 0.00768 AC: 2675 AN: 348280 Hom.: 26 AF XY: 0.00737 AC XY: 1369 AN XY: 185630

Gnomad4 AFR exome AF: 0.00367

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00284

Gnomad4 EAS exome AF: 0.00218

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.0241

Gnomad4 NFE exome AF: 0.00857

Gnomad4 OTH exome AF: 0.00675

GnomAD4 genome AF: 0.0110 AC: 1204 AN: 109114 Hom.: 17 Cov.: 0 AF XY: 0.0120 AC XY: 634 AN XY: 52648

Gnomad4 AFR AF: 0.00456

Gnomad4 AMR AF: 0.00410

Gnomad4 ASJ AF: 0.00702

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.00443

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.00353

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;