rs10497853

Variant names:

• chr2-200610434-A-G
• rs10497853
• NM_001159.4:c.1154-950A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOX1	NM_001159.4	MANE Select	c.1154-950A>G		intron	N/A	NP_001150.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOX1	ENST00000374700.7	TSL:1 MANE Select	c.1154-950A>G		intron	N/A	ENSP00000363832.2
	AOX1	ENST00000485106.5	TSL:1	n.172+1020A>G		intron	N/A
	AOX1	ENST00000465297.5	TSL:2	n.195+1020A>G		intron	N/A

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

African (AFR) AF: 0.0153 AC: 635 AN: 41580

American (AMR) AF: 0.0960 AC: 1468 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3466

East Asian (EAS) AF: 0.0819 AC: 424 AN: 5180

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4822

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5357 AN: 68014

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0770 Hom.: 434

Bravo AF: 0.0618

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10497853; hg19: chr2-201475157;