3-58529839-G-T

Variant names:

• chr3-58529839-G-T
• rs4681690
• NM_003500.4:c.992+627C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACOX2 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 6

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.992+627C>A		intron_variant	Intron 8 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.1190+627C>A		intron_variant	Intron 8 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.992+627C>A		intron_variant	Intron 8 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.698+627C>A		intron_variant	Intron 7 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.992+627C>A		intron_variant	Intron 8 of 14	1	NM_003500.4	ENSP00000307697.5
ACOX2	ENST00000459701.6	c.950+627C>A		intron_variant	Intron 8 of 14	5		ENSP00000418562.2
ACOX2	ENST00000489472.1	n.*48-883C>A		intron_variant	Intron 3 of 5	5		ENSP00000418515.1

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

African (AFR) AF: 0.428 AC: 17738 AN: 41462

American (AMR) AF: 0.806 AC: 12316 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2916 AN: 3472

East Asian (EAS) AF: 0.760 AC: 3935 AN: 5176

South Asian (SAS) AF: 0.846 AC: 4082 AN: 4826

European-Finnish (FIN) AF: 0.812 AC: 8603 AN: 10594

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.835 AC: 56783 AN: 67994

Other (OTH) AF: 0.757 AC: 1596 AN: 2108

Alfa AF: 0.811 Hom.: 85594

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
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4681690; hg19: chr3-58515566;