10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG

Variant names:

• chr10-45374099-T-TGCGGGGGCGGGGGCGGGG
• rs59439148
• NM_000698.5:c.-181_-180insGCGGGGGCGGGGGCGGGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000698.5(ALOX5):​c.-181_-180insGCGGGGGCGGGGGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 821,980 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000082 (1 hom.)
• Consequence: ALOX5 NM_000698.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 96 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000627 AC: 94 AN: 149894 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000924

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00620

Gnomad SAS AF: 0.000637

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000223

Gnomad OTH AF: 0.000970

GnomAD4 exome AF: 0.0000818 AC: 55 AN: 671984 Hom.: 1 AF XY: 0.0000952 AC XY: 31 AN XY: 325620

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000562

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000795

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.000559

GnomAD4 genome AF: 0.000640 AC: 96 AN: 149996 Hom.: 0 Cov.: 22 AF XY: 0.000711 AC XY: 52 AN XY: 73144

Gnomad4 AFR AF: 0.000805

Gnomad4 AMR AF: 0.000923

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00601

Gnomad4 SAS AF: 0.000638

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000223

Gnomad4 OTH AF: 0.000960

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59439148; hg19: chr10-45869547;