rs17751306

Variant names:

• chr13-70139294-G-A
• rs17751306
• ENST00000414504.6:n.1013G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-70139294-G-A
• chr13-70139294-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NR_002717.3(ATXN8OS):​n.805G>A 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 0.0173 in 528,636 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (23 hom., cov: 31)
  • Exomes 𝑓: 0.017 (97 hom.)
• Consequence: ATXN8OS NR_002717.3 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.48
• Publications: 0 publications found

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

ATXN8 (HGNC:32925):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 13-70139294-G-A is Benign according to our data. Variant chr13-70139294-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038111.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0172 (2618/151880) while in subpopulation NFE AF = 0.0256 (1738/67976). AF 95% confidence interval is 0.0246. There are 23 homozygotes in GnomAd4. There are 1245 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2618 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_002717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	NR_002717.3		n.805G>A		non_coding_transcript_exon	Exon 5 of 5
	ATXN8OS	NR_185834.1		n.454-8061G>A		intron	N/A
	ATXN8OS	NR_185835.1		n.454-8061G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	ENST00000414504.6	TSL:5	n.1013G>A		non_coding_transcript_exon	Exon 5 of 5
	ATXN8	ENST00000673087.1		n.138C>T		non_coding_transcript_exon	Exon 1 of 1
	ATXN8OS	ENST00000756272.1		n.678G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2617 AN: 151766 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.00409

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0174 AC: 6543 AN: 376756 Hom.: 97 Cov.: 0 AF XY: 0.0170 AC XY: 3390 AN XY: 199124

African (AFR) AF: 0.00295 AC: 31 AN: 10508

American (AMR) AF: 0.0136 AC: 247 AN: 18182

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 258 AN: 13220

East Asian (EAS) AF: 0.0000706 AC: 2 AN: 28328

South Asian (SAS) AF: 0.00498 AC: 126 AN: 25322

European-Finnish (FIN) AF: 0.0225 AC: 577 AN: 25660

Middle Eastern (MID) AF: 0.0128 AC: 22 AN: 1720

European-Non Finnish (NFE) AF: 0.0211 AC: 4900 AN: 231804

Other (OTH) AF: 0.0173 AC: 380 AN: 22012

GnomAD4 genome AF: 0.0172 AC: 2618 AN: 151880 Hom.: 23 Cov.: 31 AF XY: 0.0168 AC XY: 1245 AN XY: 74230

African (AFR) AF: 0.00408 AC: 169 AN: 41430

American (AMR) AF: 0.0162 AC: 247 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00978 AC: 47 AN: 4806

European-Finnish (FIN) AF: 0.0276 AC: 291 AN: 10534

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0256 AC: 1738 AN: 67976

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00661 Hom.: 2

Bravo AF: 0.0159

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATXN8OS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.099
DANN	Benign	0.60
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs17751306; hg19: chr13-70713426;