Genetic Variant ALOX5:c.1273-247T>C (chr10-45442791-T-C) – 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.1273-247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 517,548 control chromosomes in the GnomAD database, including 122,324 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 0.69 ( 36312 hom., cov: 34)

Exomes 𝑓: 0.68 ( 86012 hom. )

Consequence

ALOX5
NM_000698.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.413

Publications

8 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=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.1273-247T>C		intron_variant	Intron 9 of 13	ENST00000374391.7	NP_000689.1	P09917-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALOX5	ENST00000374391.7 link	c.1273-247T>C	intron_variant	Intron 9 of 13	1	NM_000698.5	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5 link	c.1273-247T>C	intron_variant	Intron 9 of 12	1		ENSP00000437634.1	P09917-2
ALOX5	ENST00000493336.1 link	n.179T>C	non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104845

AN:

152020

Hom.:

36282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.684

AC:

249840

AN:

365410

Hom.:

86012

Cov.:

AF XY:

0.680

AC XY:

128949

AN XY:

189644

show subpopulations

African (AFR)

AF:

0.664

AC:

6614

AN:

9960

American (AMR)

AF:

0.766

AC:

9897

AN:

12924

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

7682

AN:

11698

East Asian (EAS)

AF:

0.668

AC:

17264

AN:

25836

South Asian (SAS)

AF:

0.610

AC:

17461

AN:

28630

European-Finnish (FIN)

AF:

0.723

AC:

18725

AN:

25910

Middle Eastern (MID)

AF:

0.684

AC:

1169

AN:

1708

European-Non Finnish (NFE)

AF:

0.687

AC:

155648

AN:

226564

Other (OTH)

AF:

0.693

AC:

15380

AN:

22180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3643

7286

10930

14573

18216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.690

AC:

104923

AN:

152138

Hom.:

36312

Cov.:

AF XY:

0.689

AC XY:

51270

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.677

AC:

28099

AN:

41510

American (AMR)

AF:

0.741

AC:

11342

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2220

AN:

3472

East Asian (EAS)

AF:

0.730

AC:

3763

AN:

5152

South Asian (SAS)

AF:

0.603

AC:

2914

AN:

4832

European-Finnish (FIN)

AF:

0.734

AC:

7783

AN:

10598

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.684

AC:

46506

AN:

67960

Other (OTH)

AF:

0.689

AC:

1456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1772

3544

5316

7088

8860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.699

Hom.:

4835

Bravo

AF:

0.691

Asia WGS

AF:

0.680

AC:

2365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.7

(source)

DANN

Benign

0.40

PhyloP100

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over