2-200659013-A-G

Variant names:

• chr2-200659013-A-G
• rs10931910
• NM_001159.4:c.3172-152A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001159.4(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 NM_001159.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 5 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=-0.92).
• 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 rank	MANE	Protein	UniProt
AOX1	NM_001159.4	c.3172-152A>G		intron_variant	Intron 27 of 34	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.3172-152A>G		intron_variant	Intron 27 of 34	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000485106.5	n.1911-152A>G		intron_variant	Intron 14 of 21	1
AOX1	ENST00000465297.5	n.2104-152A>G		intron_variant	Intron 15 of 22	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

African (AFR) AF: 0.611 AC: 6516 AN: 10672

American (AMR) AF: 0.566 AC: 6229 AN: 11004

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 4572 AN: 11700

East Asian (EAS) AF: 0.778 AC: 19081 AN: 24528

South Asian (SAS) AF: 0.508 AC: 14682 AN: 28928

European-Finnish (FIN) AF: 0.507 AC: 14929 AN: 29462

Middle Eastern (MID) AF: 0.488 AC: 1519 AN: 3112

European-Non Finnish (NFE) AF: 0.419 AC: 135024 AN: 322476

Other (OTH) AF: 0.488 AC: 12106 AN: 24814

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

African (AFR) AF: 0.605 AC: 25074 AN: 41474

American (AMR) AF: 0.547 AC: 8363 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3468

East Asian (EAS) AF: 0.835 AC: 4308 AN: 5160

South Asian (SAS) AF: 0.520 AC: 2508 AN: 4820

European-Finnish (FIN) AF: 0.528 AC: 5583 AN: 10568

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28698 AN: 67974

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.453 Hom.: 23348

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
PhyloP100		0.16
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: rs10931910; hg19: chr2-201523736;