Genetic Variant ALOX5:c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG (chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-T) – 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.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000608 in 821,890 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as drug response,risk factor (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

ALOX5
NM_000698.5 upstream_gene

Scores

Not classified

Clinical Significance

drug response; risk factor no assertion criteria provided O:2

Conservation

PhyloP100: 0.984

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG		upstream_gene_variant		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.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG		upstream_gene_variant		1	NM_000698.5	ENSP00000363512.2		P09917-1
ALOX5	ENST00000542434.5 link	c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG		upstream_gene_variant		1		ENSP00000437634.1		P09917-2

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

149892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

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

GnomAD4 exome

AF:

0.00000446

AC:

AN:

671998

Hom.:

AF XY:

0.00000614

AC XY:

AN XY:

325624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13364

American (AMR)

AF:

0.00

AC:

AN:

7114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10716

East Asian (EAS)

AF:

0.00

AC:

AN:

21394

South Asian (SAS)

AF:

0.00

AC:

AN:

12728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2090

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

555282

Other (OTH)

AF:

0.00

AC:

AN:

28634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149892

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73032

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40864

American (AMR)

AF:

0.0000660

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:

10316

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: drug response; risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Atherosclerosis, susceptibility to

Other:1

Jan 01, 2004

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Asthma, diminished response to antileukotriene treatment in

Other:1

Jan 01, 2004

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.98

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over