dbSNP rs10162089: ALOX5AP:c.71-1459G>A (chr13-30742601-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_001629.4(ALOX5AP):c.71-1459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,932 control chromosomes in the GnomAD database, including 16,042 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 0.46 ( 16040 hom., cov: 31)

Exomes 𝑓: 0.70 ( 2 hom. )

Consequence

ALOX5AP
NM_001629.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.917

Publications

16 publications found

Variant links:

Genes affected

ALOX5AP (HGNC:436): (arachidonate 5-lipoxygenase activating protein) This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

ALOX5AP links:

LOC124903146 (HGNC:):

LOC124903146 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	NM_001629.4	MANE Select	c.71-1459G>A		intron	N/A	NP_001620.2
	ALOX5AP	NM_001204406.2		c.242-1459G>A		intron	N/A	NP_001191335.1	A0A087WW23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOX5AP	ENST00000380490.5	TSL:1 MANE Select	c.71-1459G>A	intron	N/A	ENSP00000369858.3	P20292
ALOX5AP	ENST00000617770.4	TSL:1	c.242-1459G>A	intron	N/A	ENSP00000479870.1	A0A087WW23
ALOX5AP	ENST00000892335.1		c.71-1459G>A	intron	N/A	ENSP00000562394.1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69219

AN:

151804

Hom.:

16035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.700

AC:

AN:

Hom.:

AF XY:

0.700

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000468493), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.308

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.456

AC:

69250

AN:

151922

Hom.:

16040

Cov.:

AF XY:

0.448

AC XY:

33227

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.487

AC:

20172

AN:

41398

American (AMR)

AF:

0.369

AC:

5638

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1440

AN:

3468

East Asian (EAS)

AF:

0.279

AC:

1433

AN:

5132

South Asian (SAS)

AF:

0.366

AC:

1767

AN:

4828

European-Finnish (FIN)

AF:

0.476

AC:

5022

AN:

10550

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32434

AN:

67954

Other (OTH)

AF:

0.433

AC:

913

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1912

3823

5735

7646

9558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.455

Hom.:

20170

Bravo

AF:

0.447

Asia WGS

AF:

0.303

AC:

1052

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

(source)

DANN

Benign

0.48

PhyloP100

0.92

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over