rs1050884

Positions:

• chr2-200671058-T-G

Variant summary

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

The NM_001159.4(AOX1):​c.*379T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 181,014 control chromosomes in the GnomAD database, including 489 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 (398 hom., cov: 33)
  • Exomes 𝑓: 0.066 (91 hom.)
• Consequence: AOX1 NM_001159.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOX1	NM_001159.4	c.*379T>G		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.*379T>G		3_prime_UTR_variant	35/35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000485106.5	n.3135T>G		non_coding_transcript_exon_variant	22/22	1
AOX1	ENST00000439380.1	c.486+1316T>G		intron_variant		3		ENSP00000413326.1

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9461 AN: 152136 Hom.: 386 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0587

GnomAD4 exome AF: 0.0657 AC: 1890 AN: 28760 Hom.: 91 Cov.: 0 AF XY: 0.0666 AC XY: 986 AN XY: 14800

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0447

Gnomad4 SAS exome AF: 0.0983

Gnomad4 FIN exome AF: 0.0982

Gnomad4 NFE exome AF: 0.0640

Gnomad4 OTH exome AF: 0.0676

GnomAD4 genome AF: 0.0625 AC: 9509 AN: 152254 Hom.: 398 Cov.: 33 AF XY: 0.0649 AC XY: 4830 AN XY: 74436

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0669

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0618 Hom.: 589

Bravo AF: 0.0582

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.79

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: rs1050884; hg19: chr2-201535781;