rs59439148

Variant names:

• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-T
• rs59439148
• NM_000698.5:c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG

Your query was ambiguous. Multiple possible variants found:

• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-T
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG
• chr10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGGGCGGGG

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
• Clinical Significance: drug response; risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: 0.984
• Publications: 13 publications found

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

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	c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG		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_-157delGCGGGGGCGGGGGCGGGGGCGGGG		upstream_gene_variant		1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.-180_-157delGCGGGGGCGGGGGCGGGGGCGGGG		upstream_gene_variant		1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149892 Hom.: 0 Cov.: 22

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: 3 AN: 671998 Hom.: 0 AF XY: 0.00000614 AC XY: 2 AN XY: 325624

African (AFR) AF: 0.00 AC: 0 AN: 13364

American (AMR) AF: 0.00 AC: 0 AN: 7114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10716

East Asian (EAS) AF: 0.00 AC: 0 AN: 21394

South Asian (SAS) AF: 0.00 AC: 0 AN: 12728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2090

European-Non Finnish (NFE) AF: 0.00000540 AC: 3 AN: 555282

Other (OTH) AF: 0.00 AC: 0 AN: 28634

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 149892 Hom.: 0 Cov.: 22 AF XY: 0.0000137 AC XY: 1 AN XY: 73032

African (AFR) AF: 0.0000245 AC: 1 AN: 40864

American (AMR) AF: 0.0000660 AC: 1 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 4842

South Asian (SAS) AF: 0.00 AC: 0 AN: 4708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67306

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 43

ClinVar

Significance: drug response; risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

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

Other links and lift over

dbSNP: rs59439148; hg19: chr10-45869547;