dbSNP rs2228064: ALOX5:p.Thr90Thr (chr10-45382602-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000698.5(ALOX5):c.270G>A(p.Thr90Thr) 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

Publications

36 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 -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 rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.270G>A	p.Thr90Thr	synonymous_variant	Exon 2 of 14	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.270G>A	p.Thr90Thr	synonymous_variant	Exon 2 of 14	1	NM_000698.5	ENSP00000363512.2		P09917-1
ALOX5	ENST00000542434.5 link	c.270G>A	p.Thr90Thr	synonymous_variant	Exon 2 of 13	1		ENSP00000437634.1		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

GnomAD2 exomes

AF:

0.0362

AC:

9083

AN:

251184

AF XY:

0.0287

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 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

African (AFR)

AF:

0.300

AC:

10043

AN:

33474

American (AMR)

AF:

0.0499

AC:

2231

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00321

AC:

AN:

26136

East Asian (EAS)

AF:

0.0522

AC:

2073

AN:

39700

South Asian (SAS)

AF:

0.0150

AC:

1297

AN:

86254

European-Finnish (FIN)

AF:

0.0131

AC:

701

AN:

53352

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00323

AC:

3587

AN:

1112000

Other (OTH)

AF:

0.0302

AC:

1822

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1242

2483

3725

4966

6208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.0913

AC:

13898

AN:

152204

Hom.:

1862

Cov.:

AF XY:

0.0880

AC XY:

6552

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.290

AC:

12043

AN:

41476

American (AMR)

AF:

0.0555

AC:

849

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.0693

AC:

359

AN:

5184

South Asian (SAS)

AF:

0.0192

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00970

AC:

103

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00412

AC:

280

AN:

68014

Other (OTH)

AF:

0.0718

AC:

152

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

517

1033

1550

2066

2583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0306

Hom.:

2123

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

(source)

DANN

Benign

0.79

PhyloP100

-2.6

Mutation Taster

=98/2

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