chr17-8096649-A-G

Position:

chr17-8096649-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021628.3(ALOXE3):c.2114T>C(p.Ile705Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00102 in 1,457,750 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00098 ( 4 hom. )

Consequence

ALOXE3
NM_021628.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.28

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014063895).

BP6

Variant 17-8096649-A-G is Benign according to our data. Variant chr17-8096649-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0014 (213/152194) while in subpopulation AMR AF= 0.00504 (77/15284). AF 95% confidence interval is 0.00413. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALOXE3	NM_021628.3 linkuse as main transcript	c.2114T>C	p.Ile705Thr	missense_variant	16/16	ENST00000448843.7
ALOXE3	NM_001165960.1 linkuse as main transcript	c.2510T>C	p.Ile837Thr	missense_variant	16/16
ALOXE3	NM_001369446.1 linkuse as main transcript	c.2111T>C	p.Ile704Thr	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOXE3	ENST00000448843.7 linkuse as main transcript	c.2114T>C	p.Ile705Thr	missense_variant	16/16	1	NM_021628.3	P1	Q9BYJ1-1
ALOXE3	ENST00000380149.6 linkuse as main transcript	c.2114T>C	p.Ile705Thr	missense_variant	15/15	1		P1	Q9BYJ1-1
ALOXE3	ENST00000318227.4 linkuse as main transcript	c.2114T>C	p.Ile705Thr	missense_variant	16/16	2		P1	Q9BYJ1-1
ALOXE3	ENST00000583808.1 linkuse as main transcript	n.351T>C		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00123

AC:

310

AN:

251492

Hom.:

AF XY:

0.00123

AC XY:

167

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.000977

AC:

1276

AN:

1305556

Hom.:

Cov.:

AF XY:

0.000984

AC XY:

647

AN XY:

657480

show subpopulations

Gnomad4 AFR exome

AF:

0.000232

Gnomad4 AMR exome

AF:

0.00308

Gnomad4 ASJ exome

AF:

0.0000791

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000614

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000927

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152194

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00205

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00123

AC:

150

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ALOXE3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Pathogenic

0.96

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Pathogenic

0.80

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.97

.;D;.

Vest4

0.47

MVP

0.99

MPC

0.22

ClinPred

0.083

GERP RS

5.1

Varity_R

0.59

gMVP

0.79

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