2-111110433-C-A

Position:

• chr2-111110433-C-A

Variant summary

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

The NM_001142807.4(ACOXL):​c.1543-7183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,176 control chromosomes in the GnomAD database, including 3,550 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 0.21 (3550 hom., cov: 32)
• Consequence: ACOXL NM_001142807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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]

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

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOXL	NM_001142807.4	c.1543-7183C>A		intron_variant		ENST00000439055.6	NP_001136279.1
ACOXL-AS1	NR_122074.1	n.229+3706G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOXL	ENST00000439055.6	c.1543-7183C>A		intron_variant		2	NM_001142807.4	ENSP00000407761
ACOXL-AS1	ENST00000376593.2	n.47+3706G>T		intron_variant, non_coding_transcript_variant		2
MIR4435-2HG	ENST00000645030.2	n.453-73511G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32090 AN: 152058 Hom.: 3552 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.211 AC: 32087 AN: 152176 Hom.: 3550 Cov.: 32 AF XY: 0.210 AC XY: 15604 AN XY: 74388

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.188

Alfa AF: 0.228 Hom.: 8417

Bravo AF: 0.200

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11681263; hg19: chr2-111868010;