ENST00000414504.6:n.1013G>A

Variant names:

• chr13-70139294-G-A
• rs17751306
• ENST00000414504.6:n.1013G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The ENST00000414504.6(ATXN8OS):​n.1013G>A 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 0.0173 in 528,636 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (23 hom., cov: 31)
  • Exomes 𝑓: 0.017 (97 hom.)
• Consequence: ATXN8OS ENST00000414504.6 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.48

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]

ENSG00000288330 (HGNC:32925):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 13-70139294-G-A is Benign according to our data. Variant chr13-70139294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038111.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0172 (2618/151880) while in subpopulation NFE AF= 0.0256 (1738/67976). AF 95% confidence interval is 0.0246. There are 23 homozygotes in gnomad4. There are 1245 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2618 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN8OS	NR_002717.3	n.805G>A		non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1	n.454-8061G>A		intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1	n.454-8061G>A		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN8OS	ENST00000414504.6	n.1013G>A		non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1	n.138C>T		non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000660386.1	n.451-8061G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2617 AN: 151766 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.00409

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0174 AC: 6543 AN: 376756 Hom.: 97 Cov.: 0 AF XY: 0.0170 AC XY: 3390 AN XY: 199124

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.0000706

Gnomad4 SAS exome AF: 0.00498

Gnomad4 FIN exome AF: 0.0225

Gnomad4 NFE exome AF: 0.0211

Gnomad4 OTH exome AF: 0.0173

GnomAD4 genome AF: 0.0172 AC: 2618 AN: 151880 Hom.: 23 Cov.: 31 AF XY: 0.0168 AC XY: 1245 AN XY: 74230

Gnomad4 AFR AF: 0.00408

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00978

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00661 Hom.: 2

Bravo AF: 0.0159

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ATXN8OS-related disorder Benign:1

Apr 20, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.099
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17751306; hg19: chr13-70713426;