Genetic Variant ATXN8OS:n.1131_1148delTGCTGCTGCTGCTGCTGC (chr13-70139383-ACTGCTGCTGCTGCTGCTG-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000414504.6(ATXN8OS):n.1131_1148delTGCTGCTGCTGCTGCTGC 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 0.00848 in 457,394 control chromosomes in the GnomAD database, including 43 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 0)

Exomes 𝑓: 0.0077 ( 26 hom. )

Consequence

ATXN8OS
ENST00000414504.6 splice_region, non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

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:

ENSG00000288330 (HGNC:32925):

ENSG00000288330 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 1204 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.923_940delTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7943_454-7926delTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7943_454-7926delTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000414504.6 link	n.1131_1148delTGCTGCTGCTGCTGCTGC	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1 link	n.31_48delCAGCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.796_813delTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1205

AN:

109084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00411

Gnomad ASJ

AF:

0.00702

Gnomad EAS

AF:

0.00160

Gnomad SAS

AF:

0.00442

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00355

GnomAD4 exome

AF:

0.00768

AC:

2675

AN:

348280

Hom.:

AF XY:

0.00737

AC XY:

1369

AN XY:

185630

show subpopulations

African (AFR)

AF:

0.00367

AC:

AN:

7902

American (AMR)

AF:

0.00134

AC:

AN:

18668

Ashkenazi Jewish (ASJ)

AF:

0.00284

AC:

AN:

11952

East Asian (EAS)

AF:

0.00218

AC:

AN:

24778

South Asian (SAS)

AF:

0.00119

AC:

AN:

26862

European-Finnish (FIN)

AF:

0.0241

AC:

509

AN:

21162

Middle Eastern (MID)

AF:

0.00762

AC:

AN:

1574

European-Non Finnish (NFE)

AF:

0.00857

AC:

1846

AN:

215522

Other (OTH)

AF:

0.00675

AC:

134

AN:

19860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

107

214

321

428

535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0110

AC:

1204

AN:

109114

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

634

AN XY:

52648

show subpopulations

African (AFR)

AF:

0.00456

AC:

111

AN:

24360

American (AMR)

AF:

0.00410

AC:

AN:

10972

Ashkenazi Jewish (ASJ)

AF:

0.00702

AC:

AN:

2848

East Asian (EAS)

AF:

0.00161

AC:

AN:

3730

South Asian (SAS)

AF:

0.00443

AC:

AN:

3610

European-Finnish (FIN)

AF:

0.0383

AC:

249

AN:

6504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0138

AC:

752

AN:

54668

Other (OTH)

AF:

0.00353

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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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chr13-70139383-ACTGCTGCTGCTGCTGCTG-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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