chr3-58521123-C-T

Position:

• chr3-58521123-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003500.4(ACOX2):​c.1632+1373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,160 control chromosomes in the GnomAD database, including 3,121 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 0.19 (3121 hom., cov: 32)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.1632+1373G>A		intron_variant		ENST00000302819.10	NP_003491.1
ACOX2	XM_005265505.2	c.1632+1373G>A		intron_variant			XP_005265562.1
ACOX2	XM_006713340.4	c.1338+1373G>A		intron_variant			XP_006713403.1
ACOX2	XM_047449042.1	c.1830+1373G>A		intron_variant			XP_047304998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.1632+1373G>A		intron_variant		1	NM_003500.4	ENSP00000307697	P1
ACOX2	ENST00000459701.6	c.1590+1373G>A		intron_variant		5		ENSP00000418562
ACOX2	ENST00000467738.1	n.570+1373G>A		intron_variant, non_coding_transcript_variant		3
ACOX2	ENST00000481527.5	n.140+1373G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29575 AN: 152042 Hom.: 3120 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.194 AC: 29594 AN: 152160 Hom.: 3121 Cov.: 32 AF XY: 0.186 AC XY: 13804 AN XY: 74364

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.210

Alfa AF: 0.228 Hom.: 1982

Bravo AF: 0.201

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.80

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: rs7651276; hg19: chr3-58506850;