Genetic Variant ALOX5:c.1273-185G>T (chr10-45442853-G-T) – 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.1273-185G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 630,644 control chromosomes in the GnomAD database, including 148,037 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 ( 36310 hom., cov: 33)

Exomes 𝑓: 0.68 ( 111727 hom. )

Consequence

ALOX5
NM_000698.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.62

Publications

9 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:

Genome browser will be placed here

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=-0.98).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.1273-185G>T		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.1273-185G>T	intron_variant	Intron 9 of 13	1	NM_000698.5	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5 link	c.1273-185G>T	intron_variant	Intron 9 of 12	1		ENSP00000437634.1	P09917-2
ALOX5	ENST00000493336.1 link	n.241G>T	non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104822

AN:

151982

Hom.:

36279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.682

AC:

326212

AN:

478542

Hom.:

111727

Cov.:

AF XY:

0.677

AC XY:

168475

AN XY:

248694

show subpopulations

African (AFR)

AF:

0.664

AC:

8410

AN:

12660

American (AMR)

AF:

0.766

AC:

13314

AN:

17384

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

8861

AN:

13548

East Asian (EAS)

AF:

0.678

AC:

20272

AN:

29892

South Asian (SAS)

AF:

0.610

AC:

26468

AN:

43360

European-Finnish (FIN)

AF:

0.721

AC:

21146

AN:

29328

Middle Eastern (MID)

AF:

0.680

AC:

1376

AN:

2024

European-Non Finnish (NFE)

AF:

0.685

AC:

207803

AN:

303560

Other (OTH)

AF:

0.693

AC:

18562

AN:

26786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5018

10035

15053

20070

25088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1778

3556

5334

7112

8890

<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:

104902

AN:

152102

Hom.:

36310

Cov.:

AF XY:

0.689

AC XY:

51261

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.677

AC:

28070

AN:

41490

American (AMR)

AF:

0.741

AC:

11330

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2219

AN:

3464

East Asian (EAS)

AF:

0.729

AC:

3753

AN:

5148

South Asian (SAS)

AF:

0.609

AC:

2942

AN:

4832

European-Finnish (FIN)

AF:

0.734

AC:

7785

AN:

10600

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.684

AC:

46511

AN:

67964

Other (OTH)

AF:

0.689

AC:

1452

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1727

3454

5180

6907

8634

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:

0.578

Hom.:

1467

Bravo

AF:

0.691

Asia WGS

AF:

0.682

AC:

2373

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.58

(source)

DANN

Benign

0.45

PhyloP100

-2.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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