rs1127745

Variant names:

• chr3-58526510-A-G
• rs1127745
• NM_003500.4:c.1302T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-58526510-A-G
• chr3-58526510-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003500.4(ACOX2):​c.1302T>C​(p.Cys434Cys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.927
• Publications: 27 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: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1302T>C	p.Cys434Cys	synonymous	Exon 10 of 15	NP_003491.1	Q99424

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX2	ENST00000302819.10	TSL:1 MANE Select	c.1302T>C	p.Cys434Cys	synonymous	Exon 10 of 15	ENSP00000307697.5	Q99424
	ACOX2	ENST00000900718.1		c.1374T>C	p.Cys458Cys	synonymous	Exon 10 of 15	ENSP00000570777.1
	ACOX2	ENST00000900721.1		c.1326T>C	p.Cys442Cys	synonymous	Exon 10 of 15	ENSP00000570780.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38079 AN: 152050 Hom.: 8893 Cov.: 33

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

GnomAD2 exomes AF: 0.148 AC: 37104 AN: 250698 AF XY: 0.138

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 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.: 32 AF XY: 0.111 AC XY: 80608 AN XY: 727158

African (AFR) AF: 0.649 AC: 21731 AN: 33476

American (AMR) AF: 0.129 AC: 5780 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4218 AN: 26134

East Asian (EAS) AF: 0.211 AC: 8391 AN: 39698

South Asian (SAS) AF: 0.112 AC: 9630 AN: 86244

European-Finnish (FIN) AF: 0.0716 AC: 3825 AN: 53410

Middle Eastern (MID) AF: 0.227 AC: 1304 AN: 5752

European-Non Finnish (NFE) AF: 0.0901 AC: 100203 AN: 1111932

Other (OTH) AF: 0.143 AC: 8620 AN: 60384

GnomAD4 genome AF: 0.251 AC: 38187 AN: 152170 Hom.: 8940 Cov.: 33 AF XY: 0.246 AC XY: 18317 AN XY: 74392

African (AFR) AF: 0.624 AC: 25872 AN: 41494

American (AMR) AF: 0.154 AC: 2359 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5168

South Asian (SAS) AF: 0.110 AC: 529 AN: 4820

European-Finnish (FIN) AF: 0.0725 AC: 770 AN: 10614

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6304 AN: 67998

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.143 Hom.: 14379

Bravo AF: 0.276

Asia WGS AF: 0.182 AC: 632 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.8
DANN	Benign	0.63
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1127745; hg19: chr3-58512237; COSMIC: COSV57148725; COSMIC: COSV57148725;