chr17-8104098-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOXE3	NM_021628.3	MANE Select	c.1785+17C>A	intron	N/A	NP_067641.2	Q9BYJ1-1
ALOXE3	NM_001165960.1		c.2181+17C>A	intron	N/A	NP_001159432.1	Q9BYJ1-2
ALOXE3	NM_001369446.1		c.1782+17C>A	intron	N/A	NP_001356375.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOXE3	ENST00000448843.7	TSL:1 MANE Select	c.1785+17C>A	intron	N/A	ENSP00000400581.2	Q9BYJ1-1
ALOXE3	ENST00000380149.6	TSL:1	c.1785+17C>A	intron	N/A	ENSP00000369494.2	Q9BYJ1-1
ALOXE3	ENST00000318227.4	TSL:2	c.1785+17C>A	intron	N/A	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

GnomAD2 exomes

AF:

0.109

AC:

27083

AN:

247516

AF XY:

0.102

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 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

African (AFR)

AF:

0.00919

AC:

307

AN:

33402

American (AMR)

AF:

0.260

AC:

11548

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

473

AN:

26044

East Asian (EAS)

AF:

0.416

AC:

16461

AN:

39600

South Asian (SAS)

AF:

0.0926

AC:

7954

AN:

85868

European-Finnish (FIN)

AF:

0.0873

AC:

4613

AN:

52846

Middle Eastern (MID)

AF:

0.0179

AC:

103

AN:

5764

European-Non Finnish (NFE)

AF:

0.0445

AC:

49354

AN:

1108824

Other (OTH)

AF:

0.0712

AC:

4290

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3765

7531

11296

15062

18827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2254

4508

6762

9016

11270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0630

AC:

9582

AN:

152162

Hom.:

796

Cov.:

AF XY:

0.0687

AC XY:

5108

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0132

AC:

548

AN:

41534

American (AMR)

AF:

0.149

AC:

2277

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2142

AN:

5144

South Asian (SAS)

AF:

0.0937

AC:

451

AN:

4814

European-Finnish (FIN)

AF:

0.0964

AC:

1021

AN:

10596

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0431

AC:

2932

AN:

68010

Other (OTH)

AF:

0.0600

AC:

127

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

401

803

1204

1606

2007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0445

Hom.:

Bravo

AF:

0.0703

Asia WGS

AF:

0.227

AC:

788

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over