dbSNP rs79677613: ACOX1:p.Arg307Arg (chr17-75953474-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004035.7(ACOX1):c.921G>A(p.Arg307Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,988 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 7 hom., cov: 33)

Exomes 𝑓: 0.013 ( 157 hom. )

Consequence

ACOX1
NM_004035.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0760

Publications

4 publications found

Variant links:

Genes affected

ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACOX1 Gene-Disease associations (from GenCC):

peroxisomal acyl-CoA oxidase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
Mitchell syndrome
Inheritance: AD Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 17-75953474-C-T is Benign according to our data. Variant chr17-75953474-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.076 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00857 (1305/152294) while in subpopulation NFE AF = 0.0138 (936/68020). AF 95% confidence interval is 0.013. There are 7 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004035.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOX1	NM_004035.7	MANE Select	c.921G>A	p.Arg307Arg	synonymous	Exon 7 of 14	NP_004026.2
ACOX1	NM_007292.6		c.921G>A	p.Arg307Arg	synonymous	Exon 7 of 14	NP_009223.2
ACOX1	NM_001185039.2		c.807G>A	p.Arg269Arg	synonymous	Exon 7 of 14	NP_001171968.1	Q15067-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOX1	ENST00000293217.10	TSL:1 MANE Select	c.921G>A	p.Arg307Arg	synonymous	Exon 7 of 14	ENSP00000293217.4	Q15067-2
ACOX1	ENST00000301608.9	TSL:1	c.921G>A	p.Arg307Arg	synonymous	Exon 7 of 14	ENSP00000301608.4	Q15067-1
ACOX1	ENST00000949477.1		c.1119G>A	p.Arg373Arg	synonymous	Exon 9 of 16	ENSP00000619536.1

Frequencies

GnomAD3 genomes

AF:

0.00858

AC:

1306

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00853

AC:

2145

AN:

251396

AF XY:

0.00854

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.000870

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00651

GnomAD4 exome

AF:

0.0131

AC:

19098

AN:

1461694

Hom.:

157

Cov.:

AF XY:

0.0127

AC XY:

9232

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

33480

American (AMR)

AF:

0.00501

AC:

224

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26132

East Asian (EAS)

AF:

0.00267

AC:

106

AN:

39684

South Asian (SAS)

AF:

0.00424

AC:

366

AN:

86240

European-Finnish (FIN)

AF:

0.0142

AC:

759

AN:

53400

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0152

AC:

16907

AN:

1111890

Other (OTH)

AF:

0.0106

AC:

642

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1100

2200

3300

4400

5500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.00857

AC:

1305

AN:

152294

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

614

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00214

AC:

AN:

41568

American (AMR)

AF:

0.00517

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.00518

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0122

AC:

130

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

936

AN:

68020

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

136

205

273

341

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:

0.00987

Hom.:

Bravo

AF:

0.00771

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0135

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Acyl-CoA oxidase deficiency (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.076

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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