Genetic Variant ENSG00000288330:n.16_48dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG (chr13-70139383-A-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG) – 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.16_48dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG 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 0.00024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00017 ( 0 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 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.908_940dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7958_454-7926dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7958_454-7926dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000288330	ENST00000673087.1 link	n.16_48dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.781_813dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	ENST00000660386.1 link	n.451-7958_451-7926dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

109116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000370

Gnomad AMI

AF:

0.00260

Gnomad AMR

AF:

0.0000912

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000267

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000307

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000201

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000172

AC:

AN:

349196

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

186194

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000253

AC:

AN:

7908

American (AMR)

AF:

0.0000535

AC:

AN:

18694

Ashkenazi Jewish (ASJ)

AF:

0.000250

AC:

AN:

11978

East Asian (EAS)

AF:

0.000605

AC:

AN:

24792

South Asian (SAS)

AF:

0.000148

AC:

AN:

26970

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

21224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1578

European-Non Finnish (NFE)

AF:

0.000125

AC:

AN:

216152

Other (OTH)

AF:

0.000201

AC:

AN:

19900

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.393

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000238

AC:

AN:

109146

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

52666

show subpopulations

African (AFR)

AF:

0.000369

AC:

AN:

24364

American (AMR)

AF:

0.0000911

AC:

AN:

10972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2848

East Asian (EAS)

AF:

0.000268

AC:

AN:

3730

South Asian (SAS)

AF:

0.00

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.000307

AC:

AN:

6518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000201

AC:

AN:

54680

Other (OTH)

AF:

0.00

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.4

Mutation Taster

=86/14

polymorphism

(source)

Splicing

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

Publications

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13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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