Genetic Variant ATXN8OS:n.1013G>A (chr13-70139294-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NR_002717.3(ATXN8OS):n.805G>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
NR_002717.3 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.48

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 8
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ATXN8OS links:

ATXN8 (HGNC:32925):

ATXN8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 2618 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_002717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
ATXN8OS	NR_002717.3	n.805G>A	non_coding_transcript_exon	Exon 5 of 5
ATXN8OS	NR_185834.1	n.454-8061G>A	intron	N/A
ATXN8OS	NR_185835.1	n.454-8061G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ATXN8OS	ENST00000414504.6	TSL:5	n.1013G>A	non_coding_transcript_exon	Exon 5 of 5
ATXN8	ENST00000673087.1		n.138C>T	non_coding_transcript_exon	Exon 1 of 1
ATXN8OS	ENST00000756272.1		n.678G>A	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2617

AN:

151766

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0170

AC XY:

3390

AN XY:

199124

show subpopulations

African (AFR)

AF:

0.00295

AC:

AN:

10508

American (AMR)

AF:

0.0136

AC:

247

AN:

18182

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

258

AN:

13220

East Asian (EAS)

AF:

0.0000706

AC:

AN:

28328

South Asian (SAS)

AF:

0.00498

AC:

126

AN:

25322

European-Finnish (FIN)

AF:

0.0225

AC:

577

AN:

25660

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

1720

European-Non Finnish (NFE)

AF:

0.0211

AC:

4900

AN:

231804

Other (OTH)

AF:

0.0173

AC:

380

AN:

22012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

287

574

860

1147

1434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.0172

AC:

2618

AN:

151880

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1245

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.00408

AC:

169

AN:

41430

American (AMR)

AF:

0.0162

AC:

247

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5144

South Asian (SAS)

AF:

0.00978

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.0276

AC:

291

AN:

10534

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0256

AC:

1738

AN:

67976

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

125

249

374

498

623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00661

Hom.:

Bravo

AF:

0.0159

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ATXN8OS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.099

(source)

DANN

Benign

0.60

PhyloP100

-1.5

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over