chr3-58527173-T-G

Variant names:

• chr3-58527173-T-G
• rs13434020
• NM_003500.4:c.1156-517A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.8).
• 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 rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.1156-517A>C		intron_variant	Intron 9 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.1354-517A>C		intron_variant	Intron 9 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.1156-517A>C		intron_variant	Intron 9 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.862-517A>C		intron_variant	Intron 8 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.1156-517A>C		intron_variant	Intron 9 of 14	1	NM_003500.4	ENSP00000307697.5
ACOX2	ENST00000459701.6	c.1114-517A>C		intron_variant	Intron 9 of 14	5		ENSP00000418562.2
ACOX2	ENST00000459888.1	n.414-517A>C		intron_variant	Intron 1 of 1	2
ACOX2	ENST00000489472.1	n.*211-517A>C		intron_variant	Intron 4 of 5	5		ENSP00000418515.1

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

African (AFR) AF: 0.603 AC: 24886 AN: 41258

American (AMR) AF: 0.151 AC: 2313 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3466

East Asian (EAS) AF: 0.224 AC: 1146 AN: 5108

South Asian (SAS) AF: 0.110 AC: 524 AN: 4782

European-Finnish (FIN) AF: 0.0728 AC: 768 AN: 10550

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6292 AN: 67864

Other (OTH) AF: 0.226 AC: 478 AN: 2114

Alfa AF: 0.146 Hom.: 2075

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
PhyloP100		-0.14
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: rs13434020; hg19: chr3-58512900;