17-8106910-T-C

Position:

• chr17-8106910-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
ALOXE3	NM_021628.3	c.1684+1558A>G		intron_variant		ENST00000448843.7	NP_067641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7	c.1684+1558A>G		intron_variant		1	NM_021628.3	ENSP00000400581.2
ALOXE3	ENST00000380149.6	c.1684+1558A>G		intron_variant		1		ENSP00000369494.2
ALOXE3	ENST00000318227.4	c.1684+1558A>G		intron_variant		2		ENSP00000314879.4

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

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.234

Alfa AF: 0.249 Hom.: 2361

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

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: rs9892383; hg19: chr17-8010228;