Variant 17-8104098-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_021628.3(ALOXE3):c.1785+17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,609,078 control chromosomes in the GnomAD database, including 7,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 796 hom., cov: 31)

Exomes 𝑓: 0.065 ( 7169 hom. )

Consequence

ALOXE3
NM_021628.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.864

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 17-8104098-G-T is Benign according to our data. Variant chr17-8104098-G-T is described in ClinVar as [Benign]. Clinvar id is 261423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOXE3	NM_021628.3 linkuse as main transcript	c.1785+17C>A		intron_variant		ENST00000448843.7	NP_067641.2	Q9BYJ1-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ALOXE3	ENST00000448843.7 linkuse as main transcript	c.1785+17C>A	intron_variant	1	NM_021628.3	ENSP00000400581.2	Q9BYJ1-1
ALOXE3	ENST00000380149.6 linkuse as main transcript	c.1785+17C>A	intron_variant	1		ENSP00000369494.2	Q9BYJ1-1J3KPH2
ALOXE3	ENST00000318227.4 linkuse as main transcript	c.1785+17C>A	intron_variant	2		ENSP00000314879.4	Q9BYJ1-1

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9583

AN:

152044

Hom.:

798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0964

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0431

Gnomad OTH

AF:

0.0592

GnomAD3 exomes

AF:

0.109

AC:

27083

AN:

247516

Hom.:

3328

AF XY:

0.102

AC XY:

13657

AN XY:

133740

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.427

Gnomad SAS exome

AF:

0.0918

Gnomad FIN exome

AF:

0.0892

Gnomad NFE exome

AF:

0.0397

Gnomad OTH exome

AF:

0.0807

GnomAD4 exome

AF:

0.0653

AC:

95103

AN:

1456916

Hom.:

7169

Cov.:

AF XY:

0.0650

AC XY:

47132

AN XY:

724724

show subpopulations

Gnomad4 AFR exome

AF:

0.00919

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.0926

Gnomad4 FIN exome

AF:

0.0873

Gnomad4 NFE exome

AF:

0.0445

Gnomad4 OTH exome

AF:

0.0712

GnomAD4 genome

AF:

0.0630

AC:

9582

AN:

152162

Hom.:

796

Cov.:

AF XY:

0.0687

AC XY:

5108

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.0937

Gnomad4 FIN

AF:

0.0964

Gnomad4 NFE

AF:

0.0431

Gnomad4 OTH

AF:

0.0600

Alfa

AF:

0.0448

Hom.:

Bravo

AF:

0.0703

Asia WGS

AF:

0.227

AC:

788

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over