3-58529839-G-T

Variant summary

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

The NM_003500.4(ACOX2):c.992+627C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,120 control chromosomes in the GnomAD database, including 41,584 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 0.72 (41584 hom., cov: 33)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX2	NM_003500.4	c.992+627C>A		intron_variant		ENST00000302819.10
ACOX2	XM_005265505.2	c.992+627C>A		intron_variant
ACOX2	XM_006713340.4	c.698+627C>A		intron_variant
ACOX2	XM_047449042.1	c.1190+627C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10	c.992+627C>A		intron_variant		1	NM_003500.4	P1
ACOX2	ENST00000459701.6	c.950+627C>A		intron_variant		5
ACOX2	ENST00000489472.1	c.*48-883C>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108910 AN: 152002 Hom.: 41588 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.716 AC: 108931 AN: 152120 Hom.: 41584 Cov.: 33 AF XY: 0.720 AC XY: 53531 AN XY: 74390

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.757

Alfa AF: 0.819 Hom.: 66682

Bravo AF: 0.699

Asia WGS AF: 0.793 AC: 2758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.2
Dann	Benign	0.74

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: rs4681690; hg19: chr3-58515566;