rs4681689

chr3-58516981-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003500.4(ACOX2):c.1850+225G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,200 control chromosomes in the GnomAD database, including 2,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2367 hom., cov: 32)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

ACOX2 (HGNC:120): (acyl-CoA oxidase 2) The product of this gene belongs to the acyl-CoA oxidase family. It encodes the branched-chain acyl-CoA oxidase which is involved in the degradation of long branched fatty acids and bile acid intermediates in peroxisomes. Deficiency of this enzyme results in the accumulation of branched fatty acids and bile acid intermediates, and may lead to Zellweger syndrome, severe cognitive disability, and death in children. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX2	NM_003500.4	c.1850+225G>T		intron_variant		ENST00000302819.10
ACOX2	XM_005265505.2	c.1850+225G>T		intron_variant
ACOX2	XM_006713340.4	c.1556+225G>T		intron_variant
ACOX2	XM_047449042.1	c.2048+225G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10	c.1850+225G>T		intron_variant		1	NM_003500.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26341 AN: 152082 Hom.: 2363 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26367 AN: 152200 Hom.: 2367 Cov.: 32 AF XY: 0.175 AC XY: 13029 AN XY: 74394

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.153

Alfa AF: 0.184 Hom.: 3428

Bravo AF: 0.170

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.18
Dann	Benign	0.66

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: rs4681689; hg19: chr3-58502708;