rs4387990

Positions:

• chr3-58530656-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.820-18C>T		intron_variant		ENST00000302819.10	NP_003491.1
ACOX2	XM_005265505.2	c.820-18C>T		intron_variant			XP_005265562.1
ACOX2	XM_006713340.4	c.526-18C>T		intron_variant			XP_006713403.1
ACOX2	XM_047449042.1	c.1018-18C>T		intron_variant			XP_047304998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.820-18C>T		intron_variant		1	NM_003500.4	ENSP00000307697	P1
ACOX2	ENST00000459701.6	c.778-18C>T		intron_variant		5		ENSP00000418562
ACOX2	ENST00000489472.1	c.*47+595C>T		intron_variant, NMD_transcript_variant		5		ENSP00000418515

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

GnomAD3 exomes AF: 0.361 AC: 88016 AN: 243814 Hom.: 17500 AF XY: 0.369 AC XY: 48577 AN XY: 131540

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 SAS exome AF: 0.347

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

Gnomad4 AFR exome AF: 0.0696

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.400

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

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.341

Alfa AF: 0.430 Hom.: 19466

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs4387990; hg19: chr3-58516383; COSMIC: COSV57147919; COSMIC: COSV57147919;