13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

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

The NR_002717.2(ATXN8OS):​n.1146_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 (15 hom., cov: 0)
  • Exomes 𝑓: 0.019 (210 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 nfe. gnomad4 allele frequency = 0.0149 (1621/109110) while in subpopulation NFE AF= 0.0213 (1164/54662). AF 95% confidence interval is 0.0203. There are 15 homozygotes in gnomad4. There are 760 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.2	n.1146_1148dup		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000673087.1	n.48_49insCAG		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7928_500-7926dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 1623 AN: 109080 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.00770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.00267

Gnomad SAS AF: 0.00470

Gnomad FIN AF: 0.00922

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0121

GnomAD4 exome AF: 0.0189 AC: 6570 AN: 348038 Hom.: 210 Cov.: 0 AF XY: 0.0184 AC XY: 3415 AN XY: 185566

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00879

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.00832

Gnomad4 FIN exome AF: 0.00939

Gnomad4 NFE exome AF: 0.0244

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0149 AC: 1621 AN: 109110 Hom.: 15 Cov.: 0 AF XY: 0.0144 AC XY: 760 AN XY: 52644

Gnomad4 AFR AF: 0.00768

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00492

Gnomad4 EAS AF: 0.00268

Gnomad4 SAS AF: 0.00471

Gnomad4 FIN AF: 0.00922

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0120

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;