chr2-111116699-C-T

Variant names:

• chr2-111116699-C-T
• rs1837369
• NM_001142807.4:c.1543-917C>T

Variant summary

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

The NM_001142807.4(ACOXL):​c.1543-917C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,722 control chromosomes in the GnomAD database, including 14,369 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 0.43 (14369 hom., cov: 32)
• Consequence: ACOXL NM_001142807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 14 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOXL	NM_001142807.4	c.1543-917C>T		intron_variant	Intron 17 of 17	ENST00000439055.6	NP_001136279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOXL	ENST00000439055.6	c.1543-917C>T		intron_variant	Intron 17 of 17	2	NM_001142807.4	ENSP00000407761.1
ACOXL	ENST00000676595.2	c.1633-917C>T		intron_variant	Intron 18 of 18			ENSP00000503683.1
ACOXL	ENST00000441974.1	c.*41-917C>T		intron_variant	Intron 4 of 4	5		ENSP00000393823.1
MIR4435-2HG	ENST00000645030.2	n.453-79777G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64888 AN: 151604 Hom.: 14367 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.428 AC: 64910 AN: 151722 Hom.: 14369 Cov.: 32 AF XY: 0.422 AC XY: 31276 AN XY: 74096

African (AFR) AF: 0.408 AC: 16835 AN: 41302

American (AMR) AF: 0.291 AC: 4443 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3468

East Asian (EAS) AF: 0.430 AC: 2227 AN: 5176

South Asian (SAS) AF: 0.226 AC: 1082 AN: 4794

European-Finnish (FIN) AF: 0.509 AC: 5342 AN: 10498

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32404 AN: 67914

Other (OTH) AF: 0.394 AC: 828 AN: 2100

Alfa AF: 0.444 Hom.: 8819

Bravo AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1837369; hg19: chr2-111874276;