rs13434020

chr3-58527173-T-G

Variant summary

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

The NM_003500.4(ACOX2):c.1156-517A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,614 control chromosomes in the GnomAD database, including 8,355 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 0.24 (8355 hom., cov: 31)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX2	NM_003500.4	c.1156-517A>C		intron_variant		ENST00000302819.10
ACOX2	XM_005265505.2	c.1156-517A>C		intron_variant
ACOX2	XM_006713340.4	c.862-517A>C		intron_variant
ACOX2	XM_047449042.1	c.1354-517A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10	c.1156-517A>C		intron_variant		1	NM_003500.4	P1
ACOX2	ENST00000459701.6	c.1114-517A>C		intron_variant		5
ACOX2	ENST00000489472.1	c.*211-517A>C		intron_variant, NMD_transcript_variant		5
ACOX2	ENST00000459888.1	n.414-517A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37011 AN: 151498 Hom.: 8312 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.245 AC: 37113 AN: 151614 Hom.: 8355 Cov.: 31 AF XY: 0.240 AC XY: 17797 AN XY: 74096

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0728

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.226

Alfa AF: 0.132 Hom.: 1162

Bravo AF: 0.269

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.2
Dann	Benign	0.88

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: rs13434020; hg19: chr3-58512900;