rs1050887

Positions:

• chr2-200671207-G-A

Variant summary

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

The NM_001159.4(AOX1):​c.*528G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,160 control chromosomes in the GnomAD database, including 392 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 0.062 (392 hom., cov: 33)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: AOX1 NM_001159.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

AOX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOX1	NM_001159.4	c.*528G>A		3_prime_UTR_variant	35/35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.*528G>A		3_prime_UTR_variant	35/35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000439380.1	c.486+1465G>A		intron_variant		3		ENSP00000413326.1

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9333 AN: 151966 Hom.: 385 Cov.: 33

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0669

Gnomad OTH AF: 0.0570

GnomAD4 exome AF: 0.0263 AC: 2 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0616 AC: 9362 AN: 152084 Hom.: 392 Cov.: 33 AF XY: 0.0640 AC XY: 4756 AN XY: 74342

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0535

Gnomad4 SAS AF: 0.0900

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0669

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0626 Hom.: 295

Bravo AF: 0.0574

Asia WGS AF: 0.0690 AC: 239 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.63

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: rs1050887; hg19: chr2-201535930;