13-70131040-C-T

Position:

• chr13-70131040-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000424524.2(ATXN8OS):​n.871C>T 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 0.0135 in 398,454 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 32)
  • Exomes 𝑓: 0.015 (42 hom.)
• Consequence: ATXN8OS ENST00000424524.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

Genes affected

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 13-70131040-C-T is Benign according to our data. Variant chr13-70131040-C-T is described in ClinVar as [Benign]. Clinvar id is 2643840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.2	n.959+192C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN8OS	ENST00000678624.1	n.499+1156C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1774 AN: 152096 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00858

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0147 AC: 3621 AN: 246240 Hom.: 42 Cov.: 0 AF XY: 0.0145 AC XY: 1811 AN XY: 124764

Gnomad4 AFR exome AF: 0.00223

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00509

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00462

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0117 AC: 1774 AN: 152214 Hom.: 27 Cov.: 32 AF XY: 0.0128 AC XY: 950 AN XY: 74434

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0130 Hom.: 1

Bravo AF: 0.00916

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

ATXN8OS: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80107515; hg19: chr13-70705172;