dbSNP rs10751383: ALOX5:c.1273-494A>C (chr10-45442544-A-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.1273-494A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 154,744 control chromosomes in the GnomAD database, including 25,247 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 0.57 ( 24841 hom., cov: 34)

Exomes 𝑓: 0.55 ( 406 hom. )

Consequence

ALOX5
NM_000698.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.384

Publications

14 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.1273-494A>C		intron_variant	Intron 9 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ALOX5	ENST00000374391.7 link	c.1273-494A>C	intron_variant	Intron 9 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5 link	c.1273-494A>C	intron_variant	Intron 9 of 12	1		ENSP00000437634.1
ALOX5	ENST00000493336.1 link	n.-69A>C	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86355

AN:

152002

Hom.:

24806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.562

GnomAD4 exome

AF:

0.549

AC:

1440

AN:

2624

Hom.:

406

AF XY:

0.558

AC XY:

742

AN XY:

1330

show subpopulations

African (AFR)

AF:

0.481

AC:

AN:

104

American (AMR)

AF:

0.625

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

AN:

118

East Asian (EAS)

AF:

0.724

AC:

AN:

South Asian (SAS)

AF:

0.308

AC:

AN:

European-Finnish (FIN)

AF:

0.488

AC:

AN:

Middle Eastern (MID)

AF:

0.375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.557

AC:

1104

AN:

1982

Other (OTH)

AF:

0.526

AC:

AN:

152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.568

AC:

86444

AN:

152120

Hom.:

24841

Cov.:

AF XY:

0.565

AC XY:

42004

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.569

AC:

23634

AN:

41500

American (AMR)

AF:

0.643

AC:

9837

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1813

AN:

3472

East Asian (EAS)

AF:

0.683

AC:

3511

AN:

5144

South Asian (SAS)

AF:

0.443

AC:

2141

AN:

4828

European-Finnish (FIN)

AF:

0.543

AC:

5745

AN:

10584

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37910

AN:

67978

Other (OTH)

AF:

0.563

AC:

1188

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1962

3923

5885

7846

9808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.561

Hom.:

24898

Bravo

AF:

0.581

Asia WGS

AF:

0.555

AC:

1931

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.1

(source)

DANN

Benign

0.39

PhyloP100

-0.38

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