2-111033500-G-A

Variant names:

• chr2-111033500-G-A
• rs17482961
• NM_001142807.4:c.1369+1786G>A

Variant summary

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

The NM_001142807.4(ACOXL):​c.1369+1786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,142 control chromosomes in the GnomAD database, including 3,673 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 0.20 (3673 hom., cov: 32)
• Consequence: ACOXL NM_001142807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 4 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOXL	NM_001142807.4	c.1369+1786G>A		intron_variant	Intron 15 of 17	ENST00000439055.6	NP_001136279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOXL	ENST00000439055.6	c.1369+1786G>A		intron_variant	Intron 15 of 17	2	NM_001142807.4	ENSP00000407761.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30124 AN: 152024 Hom.: 3671 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.198 AC: 30136 AN: 152142 Hom.: 3673 Cov.: 32 AF XY: 0.195 AC XY: 14504 AN XY: 74380

African (AFR) AF: 0.0826 AC: 3428 AN: 41508

American (AMR) AF: 0.247 AC: 3776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5178

South Asian (SAS) AF: 0.161 AC: 776 AN: 4808

European-Finnish (FIN) AF: 0.182 AC: 1924 AN: 10578

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18191 AN: 67998

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.145 Hom.: 391

Bravo AF: 0.200

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.065
DANN	Benign	0.57
PhyloP100		-0.99
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: rs17482961; hg19: chr2-111791077; COSMIC: COSV67738616; COSMIC: COSV67738616;