Variant 10-45382602-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000698.5(ALOX5):c.270G>A(p.Thr90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,990 control chromosomes in the GnomAD database, including 3,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 1862 hom., cov: 33)

Exomes 𝑓: 0.015 ( 1803 hom. )

Consequence

ALOX5
NM_000698.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=-2.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5 linkuse as main transcript	c.270G>A	p.Thr90=	synonymous_variant	2/14	ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7 linkuse as main transcript	c.270G>A	p.Thr90=	synonymous_variant	2/14	1	NM_000698.5	P1	P09917-1
ALOX5	ENST00000542434.5 linkuse as main transcript	c.270G>A	p.Thr90=	synonymous_variant	2/13	1			P09917-2

Frequencies

GnomAD3 genomes

AF:

0.0912

AC:

13870

AN:

152086

Hom.:

1860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0555

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0695

Gnomad SAS

AF:

0.0192

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00412

Gnomad OTH

AF:

0.0726

GnomAD3 exomes

AF:

0.0362

AC:

9083

AN:

251184

Hom.:

797

AF XY:

0.0287

AC XY:

3904

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.0623

Gnomad SAS exome

AF:

0.0143

Gnomad FIN exome

AF:

0.0119

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0150

AC:

21935

AN:

1461786

Hom.:

1803

Cov.:

AF XY:

0.0138

AC XY:

10019

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.0499

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.0522

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.0302

GnomAD4 genome

AF:

0.0913

AC:

13898

AN:

152204

Hom.:

1862

Cov.:

AF XY:

0.0880

AC XY:

6552

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.0555

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.0693

Gnomad4 SAS

AF:

0.0192

Gnomad4 FIN

AF:

0.00970

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.0718

Alfa

AF:

0.0212

Hom.:

577

Bravo

AF:

0.103

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.8

DANN

Benign

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over