rs9892383

Variant names:

• chr17-8106910-T-C
• rs9892383
• NM_021628.3:c.1684+1558A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-8106910-T-C
• chr17-8106910-T-G

Variant summary

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

The NM_021628.3(ALOXE3):​c.1684+1558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,122 control chromosomes in the GnomAD database, including 4,716 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 0.24 (4716 hom., cov: 32)
• Consequence: ALOXE3 NM_021628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 3 publications found

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]

ALOXE3 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• self-healing collodion baby

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOXE3	NM_021628.3	c.1684+1558A>G		intron_variant	Intron 13 of 15	ENST00000448843.7	NP_067641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7	c.1684+1558A>G		intron_variant	Intron 13 of 15	1	NM_021628.3	ENSP00000400581.2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37061 AN: 152004 Hom.: 4716 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.244 AC: 37079 AN: 152122 Hom.: 4716 Cov.: 32 AF XY: 0.243 AC XY: 18083 AN XY: 74366

African (AFR) AF: 0.227 AC: 9406 AN: 41488

American (AMR) AF: 0.288 AC: 4400 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.0826 AC: 429 AN: 5196

South Asian (SAS) AF: 0.163 AC: 785 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2911 AN: 10560

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17837 AN: 67990

Other (OTH) AF: 0.234 AC: 495 AN: 2114

Alfa AF: 0.250 Hom.: 2609

Bravo AF: 0.243

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.61
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: rs9892383; hg19: chr17-8010228;