17-75978994-G-A

Position:

chr17-75978994-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000293217.10(ACOX1):c.80C>T(p.Pro27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00207 in 1,611,258 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P27P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 24 hom. )

Consequence

ACOX1
ENST00000293217.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.24

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:

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=0.00561586).

BP6

Variant 17-75978994-G-A is Benign according to our data. Variant chr17-75978994-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 235759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75978994-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00634 (966/152288) while in subpopulation AFR AF= 0.0186 (773/41560). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 450 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 966 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACOX1	NM_004035.7 linkuse as main transcript	c.80C>T	p.Pro27Leu	missense_variant	1/14	ENST00000293217.10	NP_004026.2
ACOX1	NM_007292.6 linkuse as main transcript	c.80C>T	p.Pro27Leu	missense_variant	1/14		NP_009223.2
ACOX1	NM_001185039.2 linkuse as main transcript	c.-209C>T		5_prime_UTR_variant	1/14		NP_001171968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217.10 linkuse as main transcript	c.80C>T	p.Pro27Leu	missense_variant	1/14	1	NM_004035.7	ENSP00000293217	A1	Q15067-2

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

954

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00328

AC:

818

AN:

249350

Hom.:

AF XY:

0.00287

AC XY:

388

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.0000985

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00883

GnomAD4 exome

AF:

0.00162

AC:

2365

AN:

1458970

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1177

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.0000791

Gnomad4 NFE exome

AF:

0.000646

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.00634

AC:

966

AN:

152288

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00751

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00328

AC:

398

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Acyl-CoA oxidase deficiency

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Jan 01, 2019	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 11, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 28, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Aug 16, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Benign

0.025

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0056

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

D;D;.

REVEL

Benign

0.11

Sift

Benign

0.090

T;T;.

Sift4G

Benign

0.20

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.17

MVP

0.70

MPC

0.66

ClinPred

0.053

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.66

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