4-8428090-A-G

Position:

• chr4-8428090-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX3	NM_003501.3	c.-14-11555T>C		intron_variant		ENST00000356406.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX3	ENST00000356406.10	c.-14-11555T>C		intron_variant		1	NM_003501.3	P1
ACOX3	ENST00000413009.6	c.-14-11555T>C		intron_variant		1
ACOX3	ENST00000503233.5	c.-15+261T>C		intron_variant		1		P1
ACOX3	ENST00000514423.1	c.-142+261T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.720

Alfa AF: 0.705 Hom.: 42587

Bravo AF: 0.732

Asia WGS AF: 0.739 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2631731; hg19: chr4-8429817;