rs3027232

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000318227.4(ALOXE3):c.-365C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,537,118 control chromosomes in the GnomAD database, including 55,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6683 hom., cov: 33)

Exomes 𝑓: 0.25 ( 49113 hom. )

Consequence

ALOXE3
ENST00000318227.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.194

Publications

24 publications found

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 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

ALOXE3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.040731E-4).

BP6

Variant 17-8118747-G-A is Benign according to our data. Variant chr17-8118747-G-A is described in ClinVar as [Benign]. Clinvar id is 1188973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOXE3	NM_001165960.1 link	c.32C>T	p.Pro11Leu	missense_variant	Exon 1 of 16		NP_001159432.1	Q9BYJ1-2
ALOXE3	NM_021628.3 link	c.-575C>T		upstream_gene_variant		ENST00000448843.7	NP_067641.2	Q9BYJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7 link	c.-575C>T		upstream_gene_variant		1	NM_021628.3	ENSP00000400581.2		Q9BYJ1-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43242

AN:

152068

Hom.:

6661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.290

GnomAD2 exomes

AF:

0.334

AC:

47376

AN:

141824

AF XY:

0.330

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.530

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.253

AC:

350482

AN:

1384932

Hom.:

49113

Cov.:

AF XY:

0.257

AC XY:

175891

AN XY:

683396

show subpopulations

African (AFR)

AF:

0.336

AC:

10600

AN:

31594

American (AMR)

AF:

0.506

AC:

18064

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7533

AN:

25180

East Asian (EAS)

AF:

0.517

AC:

18461

AN:

35734

South Asian (SAS)

AF:

0.402

AC:

31833

AN:

79234

European-Finnish (FIN)

AF:

0.210

AC:

7352

AN:

35004

Middle Eastern (MID)

AF:

0.320

AC:

1824

AN:

5696

European-Non Finnish (NFE)

AF:

0.221

AC:

238832

AN:

1078880

Other (OTH)

AF:

0.276

AC:

15983

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16619

33238

49858

66477

83096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.284

AC:

43287

AN:

152186

Hom.:

6683

Cov.:

AF XY:

0.290

AC XY:

21566

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.319

AC:

13261

AN:

41518

American (AMR)

AF:

0.409

AC:

6255

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1026

AN:

3470

East Asian (EAS)

AF:

0.463

AC:

2390

AN:

5164

South Asian (SAS)

AF:

0.415

AC:

2005

AN:

4830

European-Finnish (FIN)

AF:

0.209

AC:

2210

AN:

10598

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15188

AN:

67988

Other (OTH)

AF:

0.291

AC:

615

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1582

3163

4745

6326

7908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.246

Hom.:

20641

Bravo

AF:

0.299

TwinsUK

AF:

0.222

AC:

825

ALSPAC

AF:

0.216

AC:

833

ExAC

AF:

0.299

AC:

6244

Asia WGS

AF:

0.406

AC:

1411

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

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26576379) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive congenital ichthyosis 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.2

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.34

MetaRNN

Benign

0.00030

MetaSVM

Benign

-0.96

PhyloP100

0.19

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.13

REVEL

Benign

0.069

Sift

Benign

0.70

Sift4G

Pathogenic

0.0

Vest4

0.057

MPC

0.25

ClinPred

0.0083

GERP RS

-0.97

PromoterAI

0.016

Neutral

(source)

gMVP

0.33

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3027232

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over