Genetic Variant ALOX5:c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG (chr10-45374099-T-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000698.5(ALOX5):c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 149,894 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 22)

Consequence

ALOX5
NM_000698.5 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292

Publications

13 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: Uncertain_significance. The variant received 0 ACMG points.

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.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	N/A	NP_000689.1	P09917-1
ALOX5	NM_001320861.2		c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	N/A	NP_001307790.1
ALOX5	NM_001256153.3		c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	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.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	N/A	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5	TSL:1	c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	N/A	ENSP00000437634.1	P09917-2
ALOX5	ENST00000851643.1		c.-181_-180insGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG	upstream_gene	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149894

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73034

show subpopulations

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

African (AFR)

AF:

0.0000979

AC:

AN:

40864

American (AMR)

AF:

0.00

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

4842

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67306

Other (OTH)

AF:

0.00

AC:

AN:

2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000286219), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG

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