17-8110990-C-T

Variant names:

• chr17-8110990-C-T
• rs3027208
• NM_021628.3:c.957+369G>A

Variant summary

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

The NM_021628.3(ALOXE3):​c.957+369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,104 control chromosomes in the GnomAD database, including 8,443 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 0.29 (8443 hom., cov: 32)
• Consequence: ALOXE3 NM_021628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOXE3	NM_021628.3	c.957+369G>A		intron_variant	Intron 8 of 15	ENST00000448843.7	NP_067641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7	c.957+369G>A		intron_variant	Intron 8 of 15	1	NM_021628.3	ENSP00000400581.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44555 AN: 151986 Hom.: 8409 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.294 AC: 44655 AN: 152104 Hom.: 8443 Cov.: 32 AF XY: 0.296 AC XY: 22040 AN XY: 74354

African (AFR) AF: 0.523 AC: 21664 AN: 41460

American (AMR) AF: 0.309 AC: 4722 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2540 AN: 5158

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4810

European-Finnish (FIN) AF: 0.219 AC: 2322 AN: 10606

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10552 AN: 67994

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.204 Hom.: 7007

Bravo AF: 0.312

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.67
PhyloP100		-1.5
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: rs3027208; hg19: chr17-8014308;