Genetic Variant ATXN8OS:n.1128_1148delTGCTGCTGCTGCTGCTGCTGC (chr13-70139383-ACTGCTGCTGCTGCTGCTGCTG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000414504.6(ATXN8OS):n.1128_1148delTGCTGCTGCTGCTGCTGCTGC 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 0.00267 in 458,296 control chromosomes in the GnomAD database, including 13 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 0.0084 ( 12 hom., cov: 0)

Exomes 𝑓: 0.00088 ( 1 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.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0084 (917/109128) while in subpopulation AFR AF = 0.0311 (757/24352). AF 95% confidence interval is 0.0293. There are 12 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 917 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.920_940delTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7946_454-7926delTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7946_454-7926delTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000414504.6 link	n.1128_1148delTGCTGCTGCTGCTGCTGCTGC	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1 link	n.28_48delCAGCAGCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.793_813delTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

910

AN:

109098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00958

Gnomad ASJ

AF:

0.00281

Gnomad EAS

AF:

0.000267

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000153

Gnomad MID

AF:

0.00391

Gnomad NFE

AF:

0.000585

Gnomad OTH

AF:

0.00852

GnomAD4 exome

AF:

0.000876

AC:

306

AN:

349168

Hom.:

AF XY:

0.000816

AC XY:

152

AN XY:

186184

show subpopulations

African (AFR)

AF:

0.0177

AC:

140

AN:

7906

American (AMR)

AF:

0.00161

AC:

AN:

18690

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

11976

East Asian (EAS)

AF:

0.0000403

AC:

AN:

24792

South Asian (SAS)

AF:

0.0000371

AC:

AN:

26968

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

21222

Middle Eastern (MID)

AF:

0.00190

AC:

AN:

1578

European-Non Finnish (NFE)

AF:

0.000333

AC:

AN:

216140

Other (OTH)

AF:

0.00206

AC:

AN:

19896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00840

AC:

917

AN:

109128

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

490

AN XY:

52656

show subpopulations

African (AFR)

AF:

0.0311

AC:

757

AN:

24352

American (AMR)

AF:

0.00957

AC:

105

AN:

10970

Ashkenazi Jewish (ASJ)

AF:

0.00281

AC:

AN:

2848

East Asian (EAS)

AF:

0.000268

AC:

AN:

3728

South Asian (SAS)

AF:

0.00

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

6518

Middle Eastern (MID)

AF:

0.00424

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000585

AC:

AN:

54678

Other (OTH)

AF:

0.00847

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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-ACTGCTGCTGCTGCTGCTG

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