rs12430

Variant names:

• chr17-75945874-G-A
• rs12430
• NM_004035.7:c.*874C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004035.7(ACOX1):​c.*874C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,808 control chromosomes in the GnomAD database, including 1,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1020 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: ACOX1 NM_004035.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.150
• Publications: 13 publications found

Genes affected

ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACOX1 Gene-Disease associations (from GenCC):

• peroxisomal acyl-CoA oxidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Mitchell syndrome

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-75945874-G-A is Benign according to our data. Variant chr17-75945874-G-A is described in ClinVar as Benign. ClinVar VariationId is 325356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004035.7. 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
	ACOX1	NM_004035.7	MANE Select	c.*874C>T		3_prime_UTR	Exon 14 of 14	NP_004026.2
	ACOX1	NM_007292.6		c.*874C>T		3_prime_UTR	Exon 14 of 14	NP_009223.2
	ACOX1	NM_001185039.2		c.*874C>T		3_prime_UTR	Exon 14 of 14	NP_001171968.1	Q15067-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX1	ENST00000293217.10	TSL:1 MANE Select	c.*874C>T		3_prime_UTR	Exon 14 of 14	ENSP00000293217.4	Q15067-2
	ACOX1	ENST00000301608.9	TSL:1	c.*874C>T		3_prime_UTR	Exon 14 of 14	ENSP00000301608.4	Q15067-1
	ACOX1	ENST00000949477.1		c.*874C>T		3_prime_UTR	Exon 16 of 16	ENSP00000619536.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16776 AN: 151456 Hom.: 1016 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0901

GnomAD4 exome AF: 0.149 AC: 37 AN: 248 Hom.: 1 Cov.: 0 AF XY: 0.125 AC XY: 16 AN XY: 128

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.140 AC: 34 AN: 242

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.111 AC: 16787 AN: 151560 Hom.: 1020 Cov.: 32 AF XY: 0.110 AC XY: 8116 AN XY: 74034

African (AFR) AF: 0.141 AC: 5826 AN: 41322

American (AMR) AF: 0.0759 AC: 1154 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.0782 AC: 404 AN: 5168

South Asian (SAS) AF: 0.119 AC: 571 AN: 4800

European-Finnish (FIN) AF: 0.117 AC: 1216 AN: 10356

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 6985 AN: 67928

Other (OTH) AF: 0.0911 AC: 192 AN: 2108

Alfa AF: 0.103 Hom.: 1413

Bravo AF: 0.110

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Acyl-CoA oxidase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.36
PhyloP100		-0.15
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: rs12430; hg19: chr17-73941955;