Genetic Variant ATXN8OS:n.816C>T (chr13-70131040-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000424524.3(ATXN8OS):n.816C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 398,454 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 27 hom., cov: 32)

Exomes 𝑓: 0.015 ( 42 hom. )

Consequence

ATXN8OS
ENST00000424524.3 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

Publications

0 publications found

Variant links:

Genes affected

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 13-70131040-C-T is Benign according to our data. Variant chr13-70131040-C-T is described in ClinVar as Benign. ClinVar VariationId is 2643840.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1774 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424524.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ATXN8OS	NR_185841.1	MANE Select	n.816C>T	non_coding_transcript_exon	Exon 4 of 4
ATXN8OS	NR_185842.1		n.943C>T	non_coding_transcript_exon	Exon 4 of 4
ATXN8OS	NR_002717.3		n.751+192C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ATXN8OS	ENST00000424524.3	TSL:1 MANE Select	n.816C>T	non_coding_transcript_exon	Exon 4 of 4
ATXN8OS	ENST00000665905.2		n.1035C>T	non_coding_transcript_exon	Exon 4 of 4
ATXN8OS	ENST00000414504.6	TSL:5	n.959+192C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1774

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0446

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.0147

AC:

3621

AN:

246240

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1811

AN XY:

124764

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

7180

American (AMR)

AF:

0.0106

AC:

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.00509

AC:

AN:

9236

East Asian (EAS)

AF:

0.00

AC:

AN:

22872

South Asian (SAS)

AF:

0.00462

AC:

AN:

3030

European-Finnish (FIN)

AF:

0.0388

AC:

808

AN:

20824

Middle Eastern (MID)

AF:

0.0155

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.0154

AC:

2434

AN:

158004

Other (OTH)

AF:

0.0124

AC:

203

AN:

16366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

265

530

794

1059

1324

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:

0.0117

AC:

1774

AN:

152214

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

950

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41558

American (AMR)

AF:

0.00857

AC:

131

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00373

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0446

AC:

473

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0150

AC:

1019

AN:

67968

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

183

275

366

458

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:

0.0130

Hom.:

Bravo

AF:

0.00916

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.15

(source)

DANN

Benign

0.47

PhyloP100

-1.2

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over