rs1050887

Variant names:

• chr2-200671207-G-A
• rs1050887
• NM_001159.4:c.*528G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• 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 rank	MANE	Protein	UniProt
AOX1	NM_001159.4	c.*528G>A		3_prime_UTR_variant	Exon 35 of 35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.*528G>A		3_prime_UTR_variant	Exon 35 of 35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000439380.1	c.486+1465G>A		intron_variant	Intron 4 of 4	3		ENSP00000413326.1
AOX1	ENST00000485106.5	n.*71G>A		downstream_gene_variant		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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 1 AN: 8

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0192 AC: 1 AN: 52

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0235 AC: 975 AN: 41472

American (AMR) AF: 0.111 AC: 1698 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5178

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1163 AN: 10552

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0669 AC: 4548 AN: 67992

Other (OTH) AF: 0.0555 AC: 117 AN: 2108

Alfa AF: 0.0611 Hom.: 499

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
PhyloP100		-1.1
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: rs1050887; hg19: chr2-201535930;