2-200599700-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001159.4(AOX1):c.390G>A(p.Arg130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,612,600 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (51 hom.)
• Consequence: AOX1 NM_001159.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 2-200599700-G-A is Benign according to our data. Variant chr2-200599700-G-A is described in ClinVar as [Benign]. Clinvar id is 718068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOX1	NM_001159.4	c.390G>A	p.Arg130=	synonymous_variant	5/35	ENST00000374700.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOX1	ENST00000374700.7	c.390G>A	p.Arg130=	synonymous_variant	5/35	1	NM_001159.4	P1
AOX1	ENST00000454629.1	c.315G>A	p.Arg105=	synonymous_variant	5/7	5

Frequencies

GnomAD3 genomes AF: 0.00565 AC: 859 AN: 152124 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00647

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00658 AC: 1646 AN: 250338 Hom.: 18 AF XY: 0.00652 AC XY: 883 AN XY: 135344

Gnomad AFR exome AF: 0.000804

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00458

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.00749

Gnomad OTH exome AF: 0.00705

GnomAD4 exome AF: 0.00602 AC: 8798 AN: 1460358 Hom.: 51 Cov.: 31 AF XY: 0.00576 AC XY: 4183 AN XY: 726552

Gnomad4 AFR exome AF: 0.000689

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.00387

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.00607

Gnomad4 OTH exome AF: 0.00492

GnomAD4 genome AF: 0.00564 AC: 859 AN: 152242 Hom.: 13 Cov.: 32 AF XY: 0.00647 AC XY: 482 AN XY: 74444

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0269

Gnomad4 NFE AF: 0.00647

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00527 Hom.: 2

Bravo AF: 0.00395

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00373

EpiControl AF: 0.00608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	7.9
Dann	Benign	0.62

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: rs142144384; hg19: chr2-201464423;