Genetic Variant AOX1:c.*379T>G (chr2-200671058-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001159.4(AOX1):c.*379T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 181,014 control chromosomes in the GnomAD database, including 489 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 0.062 ( 398 hom., cov: 33)

Exomes 𝑓: 0.066 ( 91 hom. )

Consequence

AOX1
NM_001159.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

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.*379T>G		3_prime_UTR	Exon 35 of 35	NP_001150.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AOX1	ENST00000374700.7	TSL:1 MANE Select	c.*379T>G	3_prime_UTR	Exon 35 of 35	ENSP00000363832.2	Q06278
AOX1	ENST00000485106.5	TSL:1	n.3135T>G	non_coding_transcript_exon	Exon 22 of 22
AOX1	ENST00000854909.1		c.*379T>G	3_prime_UTR	Exon 36 of 36	ENSP00000524968.1

Frequencies

GnomAD3 genomes

AF:

0.0622

AC:

9461

AN:

152136

Hom.:

386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.0896

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0668

Gnomad OTH

AF:

0.0587

GnomAD4 exome

AF:

0.0657

AC:

1890

AN:

28760

Hom.:

Cov.:

AF XY:

0.0666

AC XY:

986

AN XY:

14800

show subpopulations

African (AFR)

AF:

0.0234

AC:

AN:

1112

American (AMR)

AF:

0.112

AC:

247

AN:

2214

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

1168

East Asian (EAS)

AF:

0.0447

AC:

AN:

1902

South Asian (SAS)

AF:

0.0983

AC:

AN:

926

European-Finnish (FIN)

AF:

0.0982

AC:

111

AN:

1130

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

130

European-Non Finnish (NFE)

AF:

0.0640

AC:

1175

AN:

18358

Other (OTH)

AF:

0.0676

AC:

123

AN:

1820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0625

AC:

9509

AN:

152254

Hom.:

398

Cov.:

AF XY:

0.0649

AC XY:

4830

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0270

AC:

1122

AN:

41548

American (AMR)

AF:

0.111

AC:

1696

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3470

East Asian (EAS)

AF:

0.0532

AC:

276

AN:

5186

South Asian (SAS)

AF:

0.0901

AC:

435

AN:

4828

European-Finnish (FIN)

AF:

0.110

AC:

1162

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0669

AC:

4547

AN:

68014

Other (OTH)

AF:

0.0572

AC:

121

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

446

892

1337

1783

2229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0616

Hom.:

958

Bravo

AF:

0.0582

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.6

(source)

DANN

Benign

0.79

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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