Genetic Variant ATXN8OS:n.1143_1148delTGCTGC (chr13-70139383-ACTGCTG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000414504.6(ATXN8OS):n.1143_1148delTGCTGC variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 440,074 control chromosomes in the GnomAD database, including 4,669 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 2441 hom., cov: 0)

Exomes 𝑓: 0.18 ( 2228 hom. )

Consequence

ATXN8OS
ENST00000414504.6 splice_region, non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

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:

ENSG00000288330 (HGNC:32925):

ENSG00000288330 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.935_940delTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7931_454-7926delTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7931_454-7926delTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000414504.6 link	n.1143_1148delTGCTGC	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1 link	n.43_48delCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.808_813delTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

23473

AN:

108134

Hom.:

2439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.175

AC:

58169

AN:

331902

Hom.:

2228

AF XY:

0.173

AC XY:

30489

AN XY:

175910

show subpopulations

African (AFR)

AF:

0.0552

AC:

432

AN:

7826

American (AMR)

AF:

0.134

AC:

2286

AN:

17012

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

2243

AN:

11364

East Asian (EAS)

AF:

0.104

AC:

2537

AN:

24432

South Asian (SAS)

AF:

0.172

AC:

4051

AN:

23586

European-Finnish (FIN)

AF:

0.170

AC:

3507

AN:

20640

Middle Eastern (MID)

AF:

0.211

AC:

324

AN:

1532

European-Non Finnish (NFE)

AF:

0.189

AC:

39058

AN:

206406

Other (OTH)

AF:

0.195

AC:

3731

AN:

19104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

1831

3662

5494

7325

9156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<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:

0.217

AC:

23482

AN:

108172

Hom.:

2441

Cov.:

AF XY:

0.217

AC XY:

11304

AN XY:

52162

show subpopulations

African (AFR)

AF:

0.0735

AC:

1783

AN:

24262

American (AMR)

AF:

0.248

AC:

2678

AN:

10812

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

752

AN:

2834

East Asian (EAS)

AF:

0.109

AC:

405

AN:

3724

South Asian (SAS)

AF:

0.351

AC:

1252

AN:

3570

European-Finnish (FIN)

AF:

0.209

AC:

1343

AN:

6428

Middle Eastern (MID)

AF:

0.267

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.271

AC:

14650

AN:

54148

Other (OTH)

AF:

0.241

AC:

337

AN:

1398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

647

1294

1942

2589

3236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

Splicing

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

Publications

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13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over