Variant rs1127745 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003500.4(ACOX2):c.1302T>C(p.Cys434=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,910 control chromosomes in the GnomAD database, including 23,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 8940 hom., cov: 33)

Exomes 𝑓: 0.11 ( 15035 hom. )

Consequence

ACOX2
NM_003500.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.927

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-58526510-A-G is Benign according to our data. Variant chr3-58526510-A-G is described in ClinVar as [Benign]. Clinvar id is 1600142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.927 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACOX2	NM_003500.4 linkuse as main transcript	c.1302T>C	p.Cys434=	synonymous_variant	10/15	ENST00000302819.10
ACOX2	XM_047449042.1 linkuse as main transcript	c.1500T>C	p.Cys500=	synonymous_variant	10/15
ACOX2	XM_005265505.2 linkuse as main transcript	c.1302T>C	p.Cys434=	synonymous_variant	10/15
ACOX2	XM_006713340.4 linkuse as main transcript	c.1008T>C	p.Cys336=	synonymous_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10 linkuse as main transcript	c.1302T>C	p.Cys434=	synonymous_variant	10/15	1	NM_003500.4	P1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38079

AN:

152050

Hom.:

8893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0725

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.148

AC:

37104

AN:

250698

Hom.:

5058

AF XY:

0.138

AC XY:

18715

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0713

Gnomad NFE exome

AF:

0.0979

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.112

AC:

163702

AN:

1461740

Hom.:

15035

Cov.:

AF XY:

0.111

AC XY:

80608

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0716

Gnomad4 NFE exome

AF:

0.0901

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.251

AC:

38187

AN:

152170

Hom.:

8940

Cov.:

AF XY:

0.246

AC XY:

18317

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0725

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.123

Hom.:

4655

Bravo

AF:

0.276

Asia WGS

AF:

0.182

AC:

632

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.8

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over