Genetic Variant ALOX5:c.555-4745G>A (chr10-45419296-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000698.5(ALOX5):c.555-4745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,344 control chromosomes in the GnomAD database, including 15,729 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 0.45 ( 15729 hom., cov: 34)

Consequence

ALOX5
NM_000698.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.555-4745G>A		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1	P09917-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7 link	c.555-4745G>A		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2		P09917-1
ALOX5	ENST00000542434.5 link	c.555-4745G>A		intron_variant	Intron 4 of 12	1		ENSP00000437634.1		P09917-2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68407

AN:

151230

Hom.:

15729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.452

AC:

68438

AN:

151344

Hom.:

15729

Cov.:

AF XY:

0.459

AC XY:

33941

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.401

AC:

16481

AN:

41102

American (AMR)

AF:

0.500

AC:

7618

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1270

AN:

3466

East Asian (EAS)

AF:

0.448

AC:

2277

AN:

5080

South Asian (SAS)

AF:

0.455

AC:

2190

AN:

4816

European-Finnish (FIN)

AF:

0.539

AC:

5691

AN:

10566

Middle Eastern (MID)

AF:

0.383

AC:

111

AN:

290

European-Non Finnish (NFE)

AF:

0.461

AC:

31240

AN:

67770

Other (OTH)

AF:

0.445

AC:

940

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1924

3847

5771

7694

9618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.425

Hom.:

3155

Bravo

AF:

0.446

Asia WGS

AF:

0.474

AC:

1650

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.91

PhyloP100

-1.0

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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chr10-45419296-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over