17-75942304-C-T

Position:

• chr17-75942304-C-T

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.*4444G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,600 control chromosomes in the GnomAD database, including 1,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1688 hom., cov: 29)
  • Exomes 𝑓: 0.042 (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: -0.942

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=-0.98).
• BP6: Variant 17-75942304-C-T is Benign according to our data. Variant chr17-75942304-C-T is described in ClinVar as [Benign]. Clinvar id is 325307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX1	NM_004035.7	c.*4444G>A		3_prime_UTR_variant	14/14	ENST00000293217.10	NP_004026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217.10	c.*4444G>A		3_prime_UTR_variant	14/14	1	NM_004035.7	ENSP00000293217	A1
ACOX1	ENST00000301608.9	c.*4444G>A		3_prime_UTR_variant	14/14	1		ENSP00000301608	P3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18355 AN: 151482 Hom.: 1684 Cov.: 29

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.113

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0417 AC: 1 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.121 AC: 18380 AN: 151600 Hom.: 1688 Cov.: 29 AF XY: 0.119 AC XY: 8826 AN XY: 74080

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.0528

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.112

Alfa AF: 0.108 Hom.: 168

Bravo AF: 0.128

Asia WGS AF: 0.0980 AC: 342 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	-0.98
CADD	Benign	1.4
DANN	Benign	0.25

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: rs7207656; hg19: chr17-73938385;