Genetic Variant AOX1:p.Arg130Arg (chr2-200599700-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001159.4(AOX1):c.390G>A(p.Arg130Arg) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.96

Publications

4 publications found

Variant links:

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]

AOX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 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 VariationId is 718068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.96 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOX1	NM_001159.4	MANE Select	c.390G>A	p.Arg130Arg	synonymous	Exon 5 of 35	NP_001150.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AOX1	ENST00000374700.7	TSL:1 MANE Select	c.390G>A	p.Arg130Arg	synonymous	Exon 5 of 35	ENSP00000363832.2	Q06278
AOX1	ENST00000854909.1		c.390G>A	p.Arg130Arg	synonymous	Exon 5 of 36	ENSP00000524968.1
AOX1	ENST00000854911.1		c.390G>A	p.Arg130Arg	synonymous	Exon 5 of 35	ENSP00000524970.1

Frequencies

GnomAD3 genomes

AF:

0.00565

AC:

859

AN:

152124

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00658

AC:

1646

AN:

250338

AF XY:

0.00652

show subpopulations

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 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.:

Cov.:

AF XY:

0.00576

AC XY:

4183

AN XY:

726552

show subpopulations

African (AFR)

AF:

0.000689

AC:

AN:

33394

American (AMR)

AF:

0.00217

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

101

AN:

26110

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39538

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.0285

AC:

1520

AN:

53374

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00607

AC:

6745

AN:

1111092

Other (OTH)

AF:

0.00492

AC:

297

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

415

830

1245

1660

2075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00564

AC:

859

AN:

152242

Hom.:

Cov.:

AF XY:

0.00647

AC XY:

482

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000915

AC:

AN:

41524

American (AMR)

AF:

0.00464

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0269

AC:

285

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00647

AC:

440

AN:

68010

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00395

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00373

EpiControl

AF:

0.00608

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.9

(source)

DANN

Benign

0.62

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over