rs1439287

Positions:

• chr2-111114320-G-A
• chr2-111114320-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142807.4(ACOXL):​c.1543-3296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,256 control chromosomes in the GnomAD database, including 13,875 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 0.42 (13839 hom., cov: 32)
  • Exomes 𝑓: 0.51 (36 hom.)
• Consequence: ACOXL NM_001142807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

Genes affected

ACOXL (HGNC:25621): (acyl-CoA oxidase like) Predicted to enable acyl-CoA oxidase activity; fatty acid binding activity; and flavin adenine dinucleotide binding activity. Predicted to be involved in fatty acid beta-oxidation using acyl-CoA oxidase and lipid homeostasis. Predicted to be located in peroxisomal matrix. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

ACOXL-AS1 (HGNC:41112): (ACOXL antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOXL	NM_001142807.4	c.1543-3296G>A		intron_variant		ENST00000439055.6	NP_001136279.1
ACOXL-AS1	NR_122074.1	n.70-22C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOXL	ENST00000439055.6	c.1543-3296G>A		intron_variant		2	NM_001142807.4	ENSP00000407761
MIR4435-2HG	ENST00000645030.2	n.453-77398C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63588 AN: 151832 Hom.: 13840 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.513 AC: 157 AN: 306 Hom.: 36 Cov.: 0 AF XY: 0.546 AC XY: 107 AN XY: 196

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.419 AC: 63605 AN: 151950 Hom.: 13839 Cov.: 32 AF XY: 0.413 AC XY: 30668 AN XY: 74266

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.387

Alfa AF: 0.444 Hom.: 20870

Bravo AF: 0.405

Asia WGS AF: 0.315 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1439287; hg19: chr2-111871897;