Genetic Variant ENSG00000288330:n.43_48dupCAGCAG (chr13-70139383-A-ACTGCTG) – 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.43_48dupCAGCAG 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 ( 16 hom., cov: 0)

Exomes 𝑓: 0.015 ( 327 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 eas. GnomAd4 allele frequency = 0.0147 (1607/109100) while in subpopulation EAS AF = 0.0257 (96/3730). AF 95% confidence interval is 0.0216. There are 16 homozygotes in GnomAd4. There are 788 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1607 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.935_940dupTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7931_454-7926dupTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7931_454-7926dupTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000288330	ENST00000673087.1 link	n.43_48dupCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.808_813dupTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	ENST00000660386.1 link	n.451-7931_451-7926dupTGCTGC	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

1606

AN:

109070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.0597

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0379

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.00884

Gnomad FIN

AF:

0.00506

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0185

GnomAD4 exome

AF:

0.0154

AC:

5359

AN:

348650

Hom.:

327

Cov.:

AF XY:

0.0150

AC XY:

2779

AN XY:

185878

show subpopulations

African (AFR)

AF:

0.0194

AC:

153

AN:

7886

American (AMR)

AF:

0.0138

AC:

257

AN:

18650

Ashkenazi Jewish (ASJ)

AF:

0.0361

AC:

431

AN:

11954

East Asian (EAS)

AF:

0.0115

AC:

285

AN:

24774

South Asian (SAS)

AF:

0.0104

AC:

281

AN:

26908

European-Finnish (FIN)

AF:

0.00896

AC:

190

AN:

21202

Middle Eastern (MID)

AF:

0.0184

AC:

AN:

1572

European-Non Finnish (NFE)

AF:

0.0157

AC:

3388

AN:

215844

Other (OTH)

AF:

0.0174

AC:

345

AN:

19860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

156

312

468

624

780

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:

0.0147

AC:

1607

AN:

109100

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

788

AN XY:

52638

show subpopulations

African (AFR)

AF:

0.0162

AC:

395

AN:

24350

American (AMR)

AF:

0.0224

AC:

246

AN:

10964

Ashkenazi Jewish (ASJ)

AF:

0.0379

AC:

108

AN:

2846

East Asian (EAS)

AF:

0.0257

AC:

AN:

3730

South Asian (SAS)

AF:

0.00886

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.00506

AC:

AN:

6516

Middle Eastern (MID)

AF:

0.0551

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0112

AC:

611

AN:

54660

Other (OTH)

AF:

0.0191

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

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-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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