Genetic Variant ENSG00000288330:n.46_48dupCAG (chr13-70139383-A-ACTG) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The ENST00000673087.1(ENSG00000288330):n.46_48dupCAG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 15 hom., cov: 0)

Exomes 𝑓: 0.019 ( 210 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:

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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 nfe. GnomAd4 allele frequency = 0.0149 (1621/109110) while in subpopulation NFE AF = 0.0213 (1164/54662). AF 95% confidence interval is 0.0203. There are 15 homozygotes in GnomAd4. There are 760 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.938_940dupTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7928_454-7926dupTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7928_454-7926dupTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000288330	ENST00000673087.1 link	n.46_48dupCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.811_813dupTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	ENST00000660386.1 link	n.451-7928_451-7926dupTGC	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

1623

AN:

109080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00267

Gnomad SAS

AF:

0.00470

Gnomad FIN

AF:

0.00922

Gnomad MID

AF:

0.0234

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0121

GnomAD4 exome

AF:

0.0189

AC:

6570

AN:

348038

Hom.:

210

Cov.:

AF XY:

0.0184

AC XY:

3415

AN XY:

185566

show subpopulations

African (AFR)

AF:

0.0126

AC:

AN:

7888

American (AMR)

AF:

0.0132

AC:

246

AN:

18626

Ashkenazi Jewish (ASJ)

AF:

0.00879

AC:

105

AN:

11940

East Asian (EAS)

AF:

0.00331

AC:

AN:

24776

South Asian (SAS)

AF:

0.00832

AC:

224

AN:

26910

European-Finnish (FIN)

AF:

0.00939

AC:

199

AN:

21186

Middle Eastern (MID)

AF:

0.0191

AC:

AN:

1568

European-Non Finnish (NFE)

AF:

0.0244

AC:

5244

AN:

215288

Other (OTH)

AF:

0.0172

AC:

341

AN:

19856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

232

463

695

926

1158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0149

AC:

1621

AN:

109110

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

760

AN XY:

52644

show subpopulations

African (AFR)

AF:

0.00768

AC:

187

AN:

24360

American (AMR)

AF:

0.0135

AC:

148

AN:

10968

Ashkenazi Jewish (ASJ)

AF:

0.00492

AC:

AN:

2846

East Asian (EAS)

AF:

0.00268

AC:

AN:

3730

South Asian (SAS)

AF:

0.00471

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.00922

AC:

AN:

6510

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0213

AC:

1164

AN:

54662

Other (OTH)

AF:

0.0120

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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