Genetic Variant ENSG00000288330:n.34_48dupCAGCAGCAGCAGCAG (chr13-70139383-A-ACTGCTGCTGCTGCTG) – 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.34_48dupCAGCAGCAGCAGCAG 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 0.0038 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0044 ( 228 hom. )

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 412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.926_940dupTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7940_454-7926dupTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7940_454-7926dupTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000288330	ENST00000673087.1 link	n.34_48dupCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.799_813dupTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	ENST00000660386.1 link	n.451-7940_451-7926dupTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

412

AN:

109094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00885

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00219

Gnomad ASJ

AF:

0.00140

Gnomad EAS

AF:

0.00988

Gnomad SAS

AF:

0.00193

Gnomad FIN

AF:

0.00230

Gnomad MID

AF:

0.0117

Gnomad NFE

AF:

0.00192

Gnomad OTH

AF:

0.00142

GnomAD4 exome

AF:

0.00436

AC:

1522

AN:

349062

Hom.:

228

Cov.:

AF XY:

0.00426

AC XY:

792

AN XY:

186124

show subpopulations

African (AFR)

AF:

0.0125

AC:

AN:

7896

American (AMR)

AF:

0.00166

AC:

AN:

18690

Ashkenazi Jewish (ASJ)

AF:

0.00159

AC:

AN:

11974

East Asian (EAS)

AF:

0.00779

AC:

193

AN:

24770

South Asian (SAS)

AF:

0.00397

AC:

107

AN:

26958

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

21206

Middle Eastern (MID)

AF:

0.00253

AC:

AN:

1578

European-Non Finnish (NFE)

AF:

0.00440

AC:

950

AN:

216090

Other (OTH)

AF:

0.00407

AC:

AN:

19900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00378

AC:

412

AN:

109124

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

191

AN XY:

52656

show subpopulations

African (AFR)

AF:

0.00883

AC:

215

AN:

24350

American (AMR)

AF:

0.00219

AC:

AN:

10968

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

2848

East Asian (EAS)

AF:

0.00992

AC:

AN:

3730

South Asian (SAS)

AF:

0.00194

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.00230

AC:

AN:

6518

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00192

AC:

105

AN:

54676

Other (OTH)

AF:

0.00141

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

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

-1.4

Mutation Taster

=100/0

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-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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