rs7651276

Variant names:

• chr3-58521123-C-T
• rs7651276
• NM_003500.4:c.1632+1373G>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.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
• Publications: 8 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=-0.68).
• 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 rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.1632+1373G>A		intron_variant	Intron 12 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.1830+1373G>A		intron_variant	Intron 12 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.1632+1373G>A		intron_variant	Intron 12 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.1338+1373G>A		intron_variant	Intron 11 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.1632+1373G>A		intron_variant	Intron 12 of 14	1	NM_003500.4	ENSP00000307697.5
ACOX2	ENST00000459701.6	c.1590+1373G>A		intron_variant	Intron 12 of 14	5		ENSP00000418562.2
ACOX2	ENST00000467738.1	n.570+1373G>A		intron_variant	Intron 3 of 5	3
ACOX2	ENST00000481527.5	n.140+1373G>A		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.167 AC: 6930 AN: 41526

American (AMR) AF: 0.184 AC: 2822 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 955 AN: 3462

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5170

South Asian (SAS) AF: 0.150 AC: 724 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1166 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16183 AN: 67974

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.225 Hom.: 2740

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
PhyloP100		2.1
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: rs7651276; hg19: chr3-58506850;