rs3027215

chr17-8115188-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021628.3(ALOXE3):c.435-131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,285,510 control chromosomes in the GnomAD database, including 6,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1257 hom., cov: 32)
  • Exomes 𝑓: 0.096 (5707 hom.)
• Consequence: ALOXE3 NM_021628.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.511

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-8115188-C-T is Benign according to our data. Variant chr17-8115188-C-T is described in ClinVar as [Benign]. Clinvar id is 1255270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOXE3	NM_021628.3	c.435-131G>A		intron_variant		ENST00000448843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOXE3	ENST00000448843.7	c.435-131G>A		intron_variant		1	NM_021628.3	P1
ALOXE3	ENST00000380149.6	c.435-131G>A		intron_variant		1		P1
ALOXE3	ENST00000318227.4	c.435-131G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18065 AN: 152170 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0964 AC: 109229 AN: 1133222 Hom.: 5707 AF XY: 0.0978 AC XY: 56051 AN XY: 572896

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0654

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0852

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.119 AC: 18078 AN: 152288 Hom.: 1257 Cov.: 32 AF XY: 0.118 AC XY: 8812 AN XY: 74468

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0753

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.123

Alfa AF: 0.103 Hom.: 1142

Bravo AF: 0.123

Asia WGS AF: 0.0960 AC: 331 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3027215; hg19: chr17-8018506;