3-58513116-C-T

Variant names:

• chr3-58513116-C-T
• rs4317122
• NM_003500.4:c.1850+4090G>A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.1850+4090G>A		intron_variant	Intron 13 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.2048+4090G>A		intron_variant	Intron 13 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.1850+4090G>A		intron_variant	Intron 13 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.1556+4090G>A		intron_variant	Intron 12 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.1850+4090G>A		intron_variant	Intron 13 of 14	1	NM_003500.4	ENSP00000307697.5

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

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.289

Alfa AF: 0.271 Hom.: 2647

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs4317122; hg19: chr3-58498843;