rs1135640

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004035.7(ACOX1):c.936C>G(p.Ile312Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,296 control chromosomes in the GnomAD database, including 343,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 26185 hom., cov: 31)

Exomes 𝑓: 0.65 ( 317329 hom. )

Consequence

ACOX1
NM_004035.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.13

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 links:

ACOX1 (HGNC:):

ACOX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0736948E-6).

BP6

Variant 17-75953459-G-C is Benign according to our data. Variant chr17-75953459-G-C is described in ClinVar as [Benign]. Clinvar id is 259223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75953459-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX1	NM_004035.7 linkuse as main transcript	c.936C>G	p.Ile312Met	missense_variant	7/14	ENST00000293217.10	NP_004026.2	Q15067-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217.10 linkuse as main transcript	c.936C>G	p.Ile312Met	missense_variant	7/14	1	NM_004035.7	ENSP00000293217.4		Q15067-2

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83314

AN:

151894

Hom.:

26185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.658

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.653

AC:

164061

AN:

251322

Hom.:

55699

AF XY:

0.655

AC XY:

88993

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.800

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.766

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.654

AC:

955479

AN:

1461284

Hom.:

317329

Cov.:

AF XY:

0.654

AC XY:

475497

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.708

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.752

Gnomad4 SAS exome

AF:

0.646

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.548

AC:

83324

AN:

152012

Hom.:

26185

Cov.:

AF XY:

0.559

AC XY:

41545

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.789

Gnomad4 SAS

AF:

0.657

Gnomad4 FIN

AF:

0.763

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.635

Hom.:

23657

Bravo

AF:

0.525

TwinsUK

AF:

0.649

AC:

2408

ALSPAC

AF:

0.658

AC:

2535

ESP6500AA

AF:

0.235

AC:

1034

ESP6500EA

AF:

0.649

AC:

5582

ExAC

AF:

0.642

AC:

77994

Asia WGS

AF:

0.665

AC:

2311

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.638

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Acyl-CoA oxidase deficiency

Benign:5

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mitchell syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.32

.;T

Eigen

Benign

-0.066

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.13

Sift

Benign

0.26

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0070

B;B

Vest4

0.28

MPC

0.65

ClinPred

0.012

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over