10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGG

Variant names:

• chr10-45374099-TGCGGGGGCGGGG-T
• rs59439148
• NM_000698.5:c.-180_-169delGCGGGGGCGGGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000698.5(ALOX5):​c.-180_-169delGCGGGGGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 821,896 control chromosomes in the GnomAD database, including 3,443 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (2469 hom., cov: 22)
  • Exomes 𝑓: 0.0099 (974 hom.)
• Consequence: ALOX5 NM_000698.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.-180_-169delGCGGGGGCGGGG		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.-180_-169delGCGGGGGCGGGG		upstream_gene_variant		1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.-180_-169delGCGGGGGCGGGG		upstream_gene_variant		1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 14902 AN: 149838 Hom.: 2464 Cov.: 22

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.000826

Gnomad SAS AF: 0.00425

Gnomad FIN AF: 0.0000969

Gnomad MID AF: 0.0194

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0786

GnomAD4 exome AF: 0.00992 AC: 6668 AN: 671956 Hom.: 974 AF XY: 0.00908 AC XY: 2955 AN XY: 325606

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.0285

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.00182

Gnomad4 SAS exome AF: 0.00652

Gnomad4 FIN exome AF: 0.0000967

Gnomad4 NFE exome AF: 0.00144

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0996 AC: 14940 AN: 149940 Hom.: 2469 Cov.: 22 AF XY: 0.0948 AC XY: 6928 AN XY: 73116

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.00203

Gnomad4 EAS AF: 0.000829

Gnomad4 SAS AF: 0.00404

Gnomad4 FIN AF: 0.0000969

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.0811

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;