17-75942275-C-CA

Position:

• chr17-75942275-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004035.7(ACOX1):​c.*4472_*4473insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,380 control chromosomes in the GnomAD database, including 3,160 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3160 hom., cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOX1 NM_004035.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.559

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 -10 ACMG points.

• BP6: Variant 17-75942275-C-CA is Benign according to our data. Variant chr17-75942275-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 325306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX1	NM_004035.7	c.*4472_*4473insT		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.*4472_*4473insT		3_prime_UTR_variant	14/14	1	NM_004035.7	ENSP00000293217	A1
ACOX1	ENST00000301608.9	c.*4472_*4473insT		3_prime_UTR_variant	14/14	1		ENSP00000301608	P3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30416 AN: 151262 Hom.: 3152 Cov.: 25

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.200

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.201 AC: 30443 AN: 151380 Hom.: 3160 Cov.: 25 AF XY: 0.197 AC XY: 14540 AN XY: 73962

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.206

Asia WGS AF: 0.187 AC: 651 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acyl-CoA oxidase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs59512794; hg19: chr17-73938356;