rs4387990

Variant names:

• chr3-58530656-G-A
• rs4387990
• NM_003500.4:c.820-18C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003500.4(ACOX2):​c.820-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,607,502 control chromosomes in the GnomAD database, including 147,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (9445 hom., cov: 34)
  • Exomes 𝑓: 0.43 (138159 hom.)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0880
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-58530656-G-A is Benign according to our data. Variant chr3-58530656-G-A is described in ClinVar as Benign. ClinVar VariationId is 1667807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.820-18C>T		intron_variant	Intron 7 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.1018-18C>T		intron_variant	Intron 7 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.820-18C>T		intron_variant	Intron 7 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.526-18C>T		intron_variant	Intron 6 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.820-18C>T		intron_variant	Intron 7 of 14	1	NM_003500.4	ENSP00000307697.5
ACOX2	ENST00000459701.6	c.778-18C>T		intron_variant	Intron 7 of 14	5		ENSP00000418562.2
ACOX2	ENST00000489472.1	n.*47+595C>T		intron_variant	Intron 3 of 5	5		ENSP00000418515.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47664 AN: 152104 Hom.: 9442 Cov.: 34

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.345

GnomAD2 exomes AF: 0.361 AC: 88016 AN: 243814 AF XY: 0.369

Gnomad AFR exome AF: 0.0779

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.0982

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.443

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.426 AC: 619691 AN: 1455280 Hom.: 138159 Cov.: 41 AF XY: 0.425 AC XY: 307192 AN XY: 723140

African (AFR) AF: 0.0696 AC: 2321 AN: 33360

American (AMR) AF: 0.354 AC: 15650 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 12358 AN: 25920

East Asian (EAS) AF: 0.112 AC: 4444 AN: 39504

South Asian (SAS) AF: 0.350 AC: 30040 AN: 85760

European-Finnish (FIN) AF: 0.340 AC: 18089 AN: 53148

Middle Eastern (MID) AF: 0.414 AC: 2380 AN: 5750

European-Non Finnish (NFE) AF: 0.461 AC: 510341 AN: 1107592

Other (OTH) AF: 0.400 AC: 24068 AN: 60096

GnomAD4 genome AF: 0.313 AC: 47667 AN: 152222 Hom.: 9445 Cov.: 34 AF XY: 0.308 AC XY: 22944 AN XY: 74412

African (AFR) AF: 0.0858 AC: 3568 AN: 41572

American (AMR) AF: 0.339 AC: 5188 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1671 AN: 3470

East Asian (EAS) AF: 0.0993 AC: 514 AN: 5178

South Asian (SAS) AF: 0.322 AC: 1556 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3569 AN: 10580

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30318 AN: 67978

Other (OTH) AF: 0.341 AC: 721 AN: 2114

Alfa AF: 0.413 Hom.: 25502

Bravo AF: 0.306

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.088
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4387990; hg19: chr3-58516383; COSMIC: COSV57147919; COSMIC: COSV57147919;