rs7215658

chr17-8106846-C-Achr17-8106846-C-G

Variant summary

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

The NM_021628.3(ALOXE3):c.1684+1622G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,668 control chromosomes in the GnomAD database, including 39,867 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 0.72 (39867 hom., cov: 32)
• Consequence: ALOXE3 NM_021628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

Genes affected

ALOXE3 (HGNC:13743): (arachidonate lipoxygenase 3) This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOXE3	NM_021628.3	c.1684+1622G>T		intron_variant		ENST00000448843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOXE3	ENST00000448843.7	c.1684+1622G>T		intron_variant		1	NM_021628.3	P1
ALOXE3	ENST00000380149.6	c.1684+1622G>T		intron_variant		1		P1
ALOXE3	ENST00000318227.4	c.1684+1622G>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109298 AN: 151550 Hom.: 39841 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.721 AC: 109368 AN: 151668 Hom.: 39867 Cov.: 32 AF XY: 0.717 AC XY: 53165 AN XY: 74138

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.718

Alfa AF: 0.759 Hom.: 89702

Bravo AF: 0.710

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.6
Dann	Benign	0.42

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: rs7215658; hg19: chr17-8010164;