Genetic Variant ALOX5:c.-181_-180insGCGGGG (chr10-45374099-T-TGCGGGG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000698.5(ALOX5):c.-181_-180insGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 821,846 control chromosomes in the GnomAD database, including 295 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 96 hom., cov: 22)

Exomes 𝑓: 0.0098 ( 199 hom. )

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.-181_-180insGCGGGG		upstream_gene_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7 link	c.-181_-180insGCGGGG		upstream_gene_variant		1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5 link	c.-181_-180insGCGGGG		upstream_gene_variant		1		ENSP00000437634.1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3546

AN:

149880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0160

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.0258

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0272

GnomAD4 exome

AF:

0.00981

AC:

6591

AN:

671864

Hom.:

199

AF XY:

0.0101

AC XY:

3281

AN XY:

325566

show subpopulations

African (AFR)

AF:

0.0151

AC:

202

AN:

13354

American (AMR)

AF:

0.0276

AC:

196

AN:

7110

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

114

AN:

10714

East Asian (EAS)

AF:

0.118

AC:

2514

AN:

21334

South Asian (SAS)

AF:

0.0166

AC:

211

AN:

12720

European-Finnish (FIN)

AF:

0.0229

AC:

474

AN:

20666

Middle Eastern (MID)

AF:

0.0191

AC:

AN:

2090

European-Non Finnish (NFE)

AF:

0.00432

AC:

2400

AN:

555256

Other (OTH)

AF:

0.0154

AC:

440

AN:

28620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

237

475

712

950

1187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0236

AC:

3539

AN:

149982

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1823

AN XY:

73138

show subpopulations

African (AFR)

AF:

0.0246

AC:

1006

AN:

40964

American (AMR)

AF:

0.0231

AC:

351

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

AN:

3448

East Asian (EAS)

AF:

0.150

AC:

722

AN:

4824

South Asian (SAS)

AF:

0.0521

AC:

245

AN:

4702

European-Finnish (FIN)

AF:

0.0223

AC:

230

AN:

10318

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0129

AC:

866

AN:

67296

Other (OTH)

AF:

0.0269

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

146

293

439

586

732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.00575

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG

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