17-75941584-T-C

Position:

• chr17-75941584-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004035.7(ACOX1):​c.*5164A>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 0.209 in 152,278 control chromosomes in the GnomAD database, including 6,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (6785 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: ACOX1 NM_004035.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.203

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-75941584-T-C is Benign according to our data. Variant chr17-75941584-T-C is described in ClinVar as [Benign]. Clinvar id is 325292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX1	NM_004035.7	c.*5164A>G		3_prime_UTR_variant	14/14	ENST00000293217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX1	ENST00000293217.10	c.*5164A>G		3_prime_UTR_variant	14/14	1	NM_004035.7	A1
ACOX1	ENST00000301608.9	c.*5164A>G		3_prime_UTR_variant	14/14	1		P3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 152096 Hom.: 6750 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.141 AC: 9 AN: 64 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 3 AN XY: 36

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.209 AC: 31873 AN: 152214 Hom.: 6785 Cov.: 32 AF XY: 0.204 AC XY: 15221 AN XY: 74436

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.184

Alfa AF: 0.103 Hom.: 1649

Bravo AF: 0.228

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Acyl-CoA oxidase deficiency Benign:1

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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs3643; hg19: chr17-73937665;