4-8428090-A-G

Variant names:

• chr4-8428090-A-G
• rs2631731
• NM_003501.3:c.-14-11555T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003501.3(ACOX3):​c.-14-11555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,234 control chromosomes in the GnomAD database, including 42,467 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 0.74 (42467 hom., cov: 34)
• Consequence: ACOX3 NM_003501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 13 publications found

Genes affected

ACOX3 (HGNC:121): (acyl-CoA oxidase 3, pristanoyl) Acyl-Coenzyme A oxidase 3 also know as pristanoyl -CoA oxidase (ACOX3)is involved in the desaturation of 2-methyl branched fatty acids in peroxisomes. Unlike the rat homolog, the human gene is expressed in very low amounts in liver such that its mRNA was undetectable by routine Northern-blot analysis or its product by immunoblotting or by enzyme activity measurements. However the human cDNA encoding a 700 amino acid protein with a peroxisomal targeting C-terminal tripeptide S-K-L was isolated and is thought to be expressed under special conditions such as specific developmental stages or in a tissue specific manner in tissues that have not yet been examined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX3	NM_003501.3	MANE Select	c.-14-11555T>C		intron	N/A	NP_003492.2
	ACOX3	NM_001375783.1		c.-15+261T>C		intron	N/A	NP_001362712.1
	ACOX3	NM_001375784.1		c.-14-11555T>C		intron	N/A	NP_001362713.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOX3	ENST00000356406.10	TSL:1 MANE Select	c.-14-11555T>C		intron	N/A	ENSP00000348775.4
	ACOX3	ENST00000503233.5	TSL:1	c.-15+261T>C		intron	N/A	ENSP00000421625.1
	ACOX3	ENST00000413009.6	TSL:1	c.-14-11555T>C		intron	N/A	ENSP00000413994.2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112682 AN: 152116 Hom.: 42417 Cov.: 34

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.741 AC: 112782 AN: 152234 Hom.: 42467 Cov.: 34 AF XY: 0.738 AC XY: 54949 AN XY: 74438

African (AFR) AF: 0.862 AC: 35839 AN: 41574

American (AMR) AF: 0.621 AC: 9500 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3300 AN: 5168

South Asian (SAS) AF: 0.841 AC: 4066 AN: 4834

European-Finnish (FIN) AF: 0.684 AC: 7242 AN: 10592

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48109 AN: 67978

Other (OTH) AF: 0.720 AC: 1521 AN: 2112

Alfa AF: 0.708 Hom.: 55455

Bravo AF: 0.732

Asia WGS AF: 0.739 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		0.20
PromoterAI		-0.19	Neutral
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: rs2631731; hg19: chr4-8429817;