rs702366

Variant names:

• chr10-45438924-G-A
• rs702366
• NM_000698.5:c.982-1506G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):​c.982-1506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,936 control chromosomes in the GnomAD database, including 19,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19901 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.982-1506G>A		intron_variant	Intron 7 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.982-1506G>A		intron_variant	Intron 7 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.982-1506G>A		intron_variant	Intron 7 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77250 AN: 151818 Hom.: 19874 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.512

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 77326 AN: 151936 Hom.: 19901 Cov.: 32 AF XY: 0.506 AC XY: 37570 AN XY: 74240

African (AFR) AF: 0.481 AC: 19907 AN: 41412

American (AMR) AF: 0.601 AC: 9184 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3258 AN: 5156

South Asian (SAS) AF: 0.418 AC: 2012 AN: 4818

European-Finnish (FIN) AF: 0.494 AC: 5209 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34284 AN: 67922

Other (OTH) AF: 0.514 AC: 1087 AN: 2114

Alfa AF: 0.508 Hom.: 66395

Bravo AF: 0.520

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.44
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs702366; hg19: chr10-45934372;