17-75953474-C-T

Position:

chr17-75953474-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004035.7(ACOX1):c.921G>A(p.Arg307=) 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

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 -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1305 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX1	NM_004035.7 linkuse as main transcript	c.921G>A	p.Arg307=	synonymous_variant	7/14	ENST00000293217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX1	ENST00000293217.10 linkuse as main transcript	c.921G>A	p.Arg307=	synonymous_variant	7/14	1	NM_004035.7	A1	Q15067-2

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

GnomAD3 exomes

AF:

0.00853

AC:

2145

AN:

251396

Hom.:

AF XY:

0.00854

AC XY:

1161

AN XY:

135892

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 SAS exome

AF:

0.00421

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

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00267

Gnomad4 SAS exome

AF:

0.00424

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.0152

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00857

AC:

1305

AN:

152294

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

614

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00771

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ACOX1: BP4, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jan 04, 2017	- -

Acyl-CoA oxidase deficiency

Benign:3

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.71

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