13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTG

Variant summary

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

The NR_002717.2(ATXN8OS):​n.1128_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 0.00267 in 458,296 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0084 (12 hom., cov: 0)
  • Exomes 𝑓: 0.00088 (1 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0084 (917/109128) while in subpopulation AFR AF= 0.0311 (757/24352). AF 95% confidence interval is 0.0293. There are 12 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 917 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN8OS	NR_002717.2	n.1128_1148del		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000673087.1	n.28_48del		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7946_500-7926del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 910 AN: 109098 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00958

Gnomad ASJ AF: 0.00281

Gnomad EAS AF: 0.000267

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000153

Gnomad MID AF: 0.00391

Gnomad NFE AF: 0.000585

Gnomad OTH AF: 0.00852

GnomAD4 exome AF: 0.000876 AC: 306 AN: 349168 Hom.: 1 AF XY: 0.000816 AC XY: 152 AN XY: 186184

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.0000403

Gnomad4 SAS exome AF: 0.0000371

Gnomad4 FIN exome AF: 0.0000942

Gnomad4 NFE exome AF: 0.000333

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00840 AC: 917 AN: 109128 Hom.: 12 Cov.: 0 AF XY: 0.00931 AC XY: 490 AN XY: 52656

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.00957

Gnomad4 ASJ AF: 0.00281

Gnomad4 EAS AF: 0.000268

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000153

Gnomad4 NFE AF: 0.000585

Gnomad4 OTH AF: 0.00847

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;