rs2241080

Positions:

• chr2-200662516-G-A
• chr2-200662516-G-T

Variant summary

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

The NM_001159.4(AOX1):​c.3429-339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,858 control chromosomes in the GnomAD database, including 6,448 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 0.28 (6448 hom., cov: 32)
• Consequence: AOX1 NM_001159.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOX1	NM_001159.4	c.3429-339G>A		intron_variant		ENST00000374700.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOX1	ENST00000374700.7	c.3429-339G>A		intron_variant		1	NM_001159.4	P1
AOX1	ENST00000485106.5	n.2168-339G>A		intron_variant, non_coding_transcript_variant		1
AOX1	ENST00000260930.10	c.87-339G>A		intron_variant		5
AOX1	ENST00000465297.5	n.2361-339G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42520 AN: 151740 Hom.: 6437 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.280 AC: 42572 AN: 151858 Hom.: 6448 Cov.: 32 AF XY: 0.289 AC XY: 21413 AN XY: 74204

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.281

Alfa AF: 0.232 Hom.: 8848

Bravo AF: 0.283

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.46

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: rs2241080; hg19: chr2-201527239;