chr17-8096639-G-A

Position:

chr17-8096639-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021628.3(ALOXE3):c.2124C>T(p.Ser708=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,385,774 control chromosomes in the GnomAD database, including 128,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12756 hom., cov: 31)

Exomes 𝑓: 0.43 ( 115753 hom. )

Consequence

ALOXE3
NM_021628.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.101

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-8096639-G-A is Benign according to our data. Variant chr17-8096639-G-A is described in ClinVar as [Benign]. Clinvar id is 261424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8096639-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.101 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALOXE3	NM_021628.3 linkuse as main transcript	c.2124C>T	p.Ser708=	synonymous_variant	16/16	ENST00000448843.7
ALOXE3	NM_001165960.1 linkuse as main transcript	c.2520C>T	p.Ser840=	synonymous_variant	16/16
ALOXE3	NM_001369446.1 linkuse as main transcript	c.2121C>T	p.Ser707=	synonymous_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOXE3	ENST00000448843.7 linkuse as main transcript	c.2124C>T	p.Ser708=	synonymous_variant	16/16	1	NM_021628.3	P1	Q9BYJ1-1
ALOXE3	ENST00000380149.6 linkuse as main transcript	c.2124C>T	p.Ser708=	synonymous_variant	15/15	1		P1	Q9BYJ1-1
ALOXE3	ENST00000318227.4 linkuse as main transcript	c.2124C>T	p.Ser708=	synonymous_variant	16/16	2		P1	Q9BYJ1-1
ALOXE3	ENST00000583808.1 linkuse as main transcript	n.361C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60491

AN:

151812

Hom.:

12738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.460

AC:

115596

AN:

251468

Hom.:

28178

AF XY:

0.452

AC XY:

61382

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.273

Gnomad AMR exome

AF:

0.663

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.637

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.427

AC:

526714

AN:

1233842

Hom.:

115753

Cov.:

AF XY:

0.424

AC XY:

265094

AN XY:

624766

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.649

Gnomad4 ASJ exome

AF:

0.449

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.398

AC:

60544

AN:

151932

Hom.:

12756

Cov.:

AF XY:

0.405

AC XY:

30068

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.543

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.414

Hom.:

26631

Bravo

AF:

0.404

Asia WGS

AF:

0.491

AC:

1707

AN:

3478

EpiCase

AF:

0.414

EpiControl

AF:

0.410

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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	- -

Autosomal recessive congenital ichthyosis 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.28

DANN

Benign

0.54

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