13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NR_002717.2(ATXN8OS):​n.1143_1148dup variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (16 hom., cov: 0)
  • Exomes 𝑓: 0.015 (327 hom.)
• Consequence: ATXN8OS NR_002717.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0147 (1607/109100) while in subpopulation EAS AF= 0.0257 (96/3730). AF 95% confidence interval is 0.0216. There are 16 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1607 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN8OS	NR_002717.2	n.1143_1148dup		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000673087.1	n.48_49insCAGCAG		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7931_500-7926dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1606 AN: 109070 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0597

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0379

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.00884

Gnomad FIN AF: 0.00506

Gnomad MID AF: 0.0508

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0185

GnomAD4 exome AF: 0.0154 AC: 5359 AN: 348650 Hom.: 327 Cov.: 0 AF XY: 0.0150 AC XY: 2779 AN XY: 185878

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.0361

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00896

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0147 AC: 1607 AN: 109100 Hom.: 16 Cov.: 0 AF XY: 0.0150 AC XY: 788 AN XY: 52638

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0379

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.00886

Gnomad4 FIN AF: 0.00506

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0191

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;