Genetic Variant ATXN8OS:n.871C>T (chr13-70131040-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

Variant links:

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]

ATXN8OS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank
ATXN8OS	NR_185841.1 link	n.816C>T	non_coding_transcript_exon_variant	Exon 4 of 4
ATXN8OS	NR_185842.1 link	n.943C>T	non_coding_transcript_exon_variant	Exon 4 of 4
ATXN8OS	NR_002717.3 link	n.751+192C>T	intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000424524.2 link	n.871C>T	non_coding_transcript_exon_variant	Exon 4 of 4	1
ATXN8OS	ENST00000665905.1 link	n.1035C>T	non_coding_transcript_exon_variant	Exon 4 of 4
ATXN8OS	ENST00000414504.6 link	n.959+192C>T	intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1774

AN:

152096

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0145

AC XY:

1811

AN XY:

124764

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

AC:

AN:

7180

Gnomad4 AMR exome

AF:

0.0106

AC:

AN:

7434

Gnomad4 ASJ exome

AF:

0.00509

AC:

AN:

9236

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

22872

Gnomad4 SAS exome

AF:

0.00462

AC:

AN:

3030

Gnomad4 FIN exome

AF:

0.0388

AC:

808

AN:

20824

Gnomad4 NFE exome

AF:

0.0154

AC:

2434

AN:

158004

Gnomad4 Remaining exome

AF:

0.0124

AC:

203

AN:

16366

Heterozygous variant carriers

265

530

794

1059

1324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0117

AC:

1774

AN:

152214

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

950

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00202

AC:

0.00202127

AN:

0.00202127

Gnomad4 AMR

AF:

0.00857

AC:

0.00857105

AN:

0.00857105

Gnomad4 ASJ

AF:

0.00605

AC:

0.00605187

AN:

0.00605187

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00373

AC:

0.00372825

AN:

0.00372825

Gnomad4 FIN

AF:

0.0446

AC:

0.0446226

AN:

0.0446226

Gnomad4 NFE

AF:

0.0150

AC:

0.0149923

AN:

0.0149923

Gnomad4 OTH

AF:

0.0128

AC:

0.012772

AN:

0.012772

Heterozygous variant carriers

183

275

366

458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.00916

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Mutation Taster

=100/0

polymorphism

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over