Variant 10-45444169-A-G 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.1728A>G(p.Pro576=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,556,424 control chromosomes in the GnomAD database, including 4,496 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 0.092 ( 868 hom., cov: 33)

Exomes 𝑓: 0.068 ( 3628 hom. )

Consequence

ALOX5
NM_000698.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.92

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=-0.74).

BP7

Synonymous conserved (PhyloP=-4.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 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.1728A>G	p.Pro576=	synonymous_variant	13/14	ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7 linkuse as main transcript	c.1728A>G	p.Pro576=	synonymous_variant	13/14	1	NM_000698.5	P1	P09917-1
ALOX5	ENST00000542434.5 linkuse as main transcript	c.1674+341A>G		intron_variant		1			P09917-2
ALOX5	ENST00000481117.1 linkuse as main transcript	n.451A>G		non_coding_transcript_exon_variant	3/3	2
ALOX5	ENST00000498461.1 linkuse as main transcript	n.559A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0919

AC:

13987

AN:

152164

Hom.:

860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0669

Gnomad OTH

AF:

0.0779

GnomAD3 exomes

AF:

0.0575

AC:

9381

AN:

163216

Hom.:

357

AF XY:

0.0539

AC XY:

4671

AN XY:

86642

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0401

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.0382

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.0762

Gnomad NFE exome

AF:

0.0627

Gnomad OTH exome

AF:

0.0492

GnomAD4 exome

AF:

0.0680

AC:

95423

AN:

1404142

Hom.:

3628

Cov.:

AF XY:

0.0663

AC XY:

45938

AN XY:

693136

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.0403

Gnomad4 ASJ exome

AF:

0.0385

Gnomad4 EAS exome

AF:

0.0871

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.0759

Gnomad4 NFE exome

AF:

0.0690

Gnomad4 OTH exome

AF:

0.0654

GnomAD4 genome

AF:

0.0920

AC:

14012

AN:

152282

Hom.:

868

Cov.:

AF XY:

0.0912

AC XY:

6789

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.0649

Gnomad4 ASJ

AF:

0.0401

Gnomad4 EAS

AF:

0.0518

Gnomad4 SAS

AF:

0.0221

Gnomad4 FIN

AF:

0.0688

Gnomad4 NFE

AF:

0.0668

Gnomad4 OTH

AF:

0.0771

Alfa

AF:

0.0745

Hom.:

264

Bravo

AF:

0.0958

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.092

DANN

Benign

0.62

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