Genetic Variant ENSG00000288330:n.25_48dupCAGCAGCAGCAGCAGCAGCAGCAG (chr13-70139383-A-ACTGCTGCTGCTGCTGCTGCTGCTG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000673087.1(ENSG00000288330):n.25_48dupCAGCAGCAGCAGCAGCAGCAGCAG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.00045 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00044 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000288330
ENST00000673087.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

0 publications found

Variant links:

Genes affected

ENSG00000288330 (HGNC:32925):

ENSG00000288330 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.917_940dupTGCTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7949_454-7926dupTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7949_454-7926dupTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000288330	ENST00000673087.1 link	n.25_48dupCAGCAGCAGCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.790_813dupTGCTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	ENST00000660386.1 link	n.451-7949_451-7926dupTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000449

AC:

AN:

109110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00187

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000165

Gnomad OTH

AF:

0.00213

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000441

AC:

154

AN:

349190

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

AN XY:

186198

show subpopulations

African (AFR)

AF:

0.000759

AC:

AN:

7908

American (AMR)

AF:

0.000749

AC:

AN:

18690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11978

East Asian (EAS)

AF:

0.00238

AC:

AN:

24790

South Asian (SAS)

AF:

0.000408

AC:

AN:

26968

European-Finnish (FIN)

AF:

0.0000471

AC:

AN:

21224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1578

European-Non Finnish (NFE)

AF:

0.000264

AC:

AN:

216156

Other (OTH)

AF:

0.000302

AC:

AN:

19898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

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:

0.000449

AC:

AN:

109140

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

AN XY:

52664

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

24360

American (AMR)

AF:

0.000273

AC:

AN:

10972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2848

East Asian (EAS)

AF:

0.00188

AC:

AN:

3730

South Asian (SAS)

AF:

0.00

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000165

AC:

AN:

54678

Other (OTH)

AF:

0.00212

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

-1.4

Splicing

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

Publications

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13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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