2-200659013-A-G

Position:

• chr2-200659013-A-G

Variant summary

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

The ENST00000374700.7(AOX1):​c.3172-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 618,762 control chromosomes in the GnomAD database, including 72,866 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 0.51 (20564 hom., cov: 32)
  • Exomes 𝑓: 0.46 (52302 hom.)
• Consequence: AOX1 ENST00000374700.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOX1	NM_001159.4	c.3172-152A>G		intron_variant		ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.3172-152A>G		intron_variant		1	NM_001159.4	ENSP00000363832	P1
AOX1	ENST00000485106.5	n.1911-152A>G		intron_variant, non_coding_transcript_variant		1
AOX1	ENST00000465297.5	n.2104-152A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77171 AN: 151948 Hom.: 20505 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.460 AC: 214658 AN: 466696 Hom.: 52302 AF XY: 0.460 AC XY: 110444 AN XY: 239860

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.778

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.508 AC: 77285 AN: 152066 Hom.: 20564 Cov.: 32 AF XY: 0.514 AC XY: 38191 AN XY: 74316

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.506

Alfa AF: 0.375 Hom.: 1336

Bravo AF: 0.520

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.44

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: rs10931910; hg19: chr2-201523736;