rs7212287

Variant names:

• chr17-75942258-T-C
• rs7212287
• NM_004035.7:c.*4490A>G

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.*4490A>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 0.124 in 149,176 control chromosomes in the GnomAD database, including 1,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1699 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOX1 NM_004035.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

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=-1.04).
• BP6: Variant 17-75942258-T-C is Benign according to our data. Variant chr17-75942258-T-C is described in ClinVar as [Benign]. Clinvar id is 325305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOX1	NM_004035.7	c.*4490A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000293217.10	NP_004026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217	c.*4490A>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_004035.7	ENSP00000293217.4
ACOX1	ENST00000301608	c.*4490A>G		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000301608.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18405 AN: 149060 Hom.: 1695 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0235

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0650

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.116

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.124 AC: 18430 AN: 149176 Hom.: 1699 Cov.: 31 AF XY: 0.122 AC XY: 8855 AN XY: 72832

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.0650

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0695

Gnomad4 OTH AF: 0.115

Alfa AF: 0.108 Hom.: 169

Bravo AF: 0.129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Acyl-CoA oxidase deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.10

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: rs7212287; hg19: chr17-73938339;