rs10497853

chr2-200610434-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001159.4(AOX1):c.1154-950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,260 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (514 hom., cov: 32)
• Consequence: AOX1 NM_001159.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

AOX1 (HGNC:553): (aldehyde oxidase 1) Aldehyde oxidase produces hydrogen peroxide and, under certain conditions, can catalyze the formation of superoxide. Aldehyde oxidase is a candidate gene for amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOX1	NM_001159.4	c.1154-950A>G		intron_variant		ENST00000374700.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOX1	ENST00000374700.7	c.1154-950A>G		intron_variant		1	NM_001159.4	P1
AOX1	ENST00000485106.5	n.172+1020A>G		intron_variant, non_coding_transcript_variant		1
AOX1	ENST00000465297.5	n.195+1020A>G		intron_variant, non_coding_transcript_variant		2
AOX1	ENST00000485965.5	n.207-950A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10298 AN: 152142 Hom.: 512 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0677 AC: 10304 AN: 152260 Hom.: 514 Cov.: 32 AF XY: 0.0708 AC XY: 5274 AN XY: 74450

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0960

Gnomad4 ASJ AF: 0.0603

Gnomad4 EAS AF: 0.0819

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0780 Hom.: 387

Bravo AF: 0.0618

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.8
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10497853; hg19: chr2-201475157;