3-58513116-C-T

Variant names:

• chr3-58513116-C-T
• rs4317122
• NM_003500.4:c.1850+4090G>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.1850+4090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,928 control chromosomes in the GnomAD database, including 7,395 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 0.31 (7395 hom., cov: 32)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003500.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX2	NM_003500.4	MANE Select	c.1850+4090G>A		intron	N/A	NP_003491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX2	ENST00000302819.10	TSL:1 MANE Select	c.1850+4090G>A		intron	N/A	ENSP00000307697.5
	ACOX2	ENST00000900718.1		c.1922+4090G>A		intron	N/A	ENSP00000570777.1
	ACOX2	ENST00000900721.1		c.1874+4090G>A		intron	N/A	ENSP00000570780.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47030 AN: 151810 Hom.: 7386 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.310 AC: 47069 AN: 151928 Hom.: 7395 Cov.: 32 AF XY: 0.312 AC XY: 23133 AN XY: 74252

African (AFR) AF: 0.337 AC: 13967 AN: 41432

American (AMR) AF: 0.286 AC: 4368 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1672 AN: 5148

South Asian (SAS) AF: 0.339 AC: 1628 AN: 4808

European-Finnish (FIN) AF: 0.355 AC: 3745 AN: 10546

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19843 AN: 67970

Other (OTH) AF: 0.289 AC: 607 AN: 2102

Alfa AF: 0.275 Hom.: 3054

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.23
PhyloP100		-1.4
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: rs4317122; hg19: chr3-58498843;