dbSNP rs934187: ALOX5:c.431+4823G>A (chr10-45400759-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.431+4823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,076 control chromosomes in the GnomAD database, including 37,430 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 0.70 ( 37430 hom., cov: 32)

Consequence

ALOX5
NM_000698.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

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:

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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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000698.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOX5	NM_000698.5	MANE Select	c.431+4823G>A	intron	N/A	NP_000689.1	P09917-1
ALOX5	NM_001320861.2		c.431+4823G>A	intron	N/A	NP_001307790.1
ALOX5	NM_001256153.3		c.431+4823G>A	intron	N/A	NP_001243082.1	P09917-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.431+4823G>A	intron	N/A	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5	TSL:1	c.431+4823G>A	intron	N/A	ENSP00000437634.1	P09917-2
ALOX5	ENST00000851643.1		c.431+4823G>A	intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105689

AN:

151958

Hom.:

37379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.678

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

GnomAD4 genome

AF:

0.696

AC:

105797

AN:

152076

Hom.:

37430

Cov.:

AF XY:

0.703

AC XY:

52286

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.815

AC:

33794

AN:

41474

American (AMR)

AF:

0.703

AC:

10738

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

1868

AN:

3470

East Asian (EAS)

AF:

0.856

AC:

4436

AN:

5180

South Asian (SAS)

AF:

0.607

AC:

2921

AN:

4814

European-Finnish (FIN)

AF:

0.753

AC:

7963

AN:

10574

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.614

AC:

41750

AN:

67964

Other (OTH)

AF:

0.677

AC:

1429

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1580

3160

4741

6321

7901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.657

Hom.:

21133

Bravo

AF:

0.700

Asia WGS

AF:

0.733

AC:

2548

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.92

(source)

DANN

Benign

0.48

PhyloP100

0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over