Variant rs2228065 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000698.5(ALOX5):c.760G>A(p.Glu254Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,613,738 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.025 ( 148 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 167 hom. )

Consequence

ALOX5
NM_000698.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Variant links:

Genes affected

ALOX5 (HGNC:435): (arachidonate 5-lipoxygenase) This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ALOX5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003055185).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.760G>A	p.Glu254Lys	missense_variant	6/14	ENST00000374391.7	NP_000689.1	P09917-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALOX5	ENST00000374391.7 link	c.760G>A	p.Glu254Lys	missense_variant	6/14	1	NM_000698.5	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5 link	c.760G>A	p.Glu254Lys	missense_variant	6/13	1		ENSP00000437634.1	P09917-2
ALOX5	ENST00000483623.2 link	n.163G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3782

AN:

151872

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00859

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0263

Gnomad SAS

AF:

0.00789

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0202

GnomAD3 exomes

AF:

0.00939

AC:

2359

AN:

251274

Hom.:

AF XY:

0.00789

AC XY:

1071

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0859

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0321

Gnomad SAS exome

AF:

0.00650

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00348

AC:

5082

AN:

1461748

Hom.:

167

Cov.:

AF XY:

0.00329

AC XY:

2389

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.00577

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.0249

AC:

3791

AN:

151990

Hom.:

148

Cov.:

AF XY:

0.0233

AC XY:

1732

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0826

Gnomad4 AMR

AF:

0.00857

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.00769

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0205

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.0282

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0840

AC:

370

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0111

AC:

1350

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.087

DANN

Benign

0.54

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.054

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.11

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.27

Sift

Benign

0.88

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0

.;B

Vest4

0.062

MPC

0.32

ClinPred

0.00077

GERP RS

-7.1

Varity_R

0.18

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over