rs1487562

Variant names:

• chr10-45433374-C-T
• rs1487562
• NM_000698.5:c.981+4610C>T

Variant summary

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

The NM_000698.5(ALOX5):​c.981+4610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,152 control chromosomes in the GnomAD database, including 3,357 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 0.20 (3357 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 22 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.981+4610C>T		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.981+4610C>T		intron_variant	Intron 7 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.981+4610C>T		intron_variant	Intron 7 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30685 AN: 152034 Hom.: 3354 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.202 AC: 30708 AN: 152152 Hom.: 3357 Cov.: 33 AF XY: 0.204 AC XY: 15157 AN XY: 74372

African (AFR) AF: 0.252 AC: 10452 AN: 41506

American (AMR) AF: 0.143 AC: 2193 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5190

South Asian (SAS) AF: 0.166 AC: 799 AN: 4812

European-Finnish (FIN) AF: 0.268 AC: 2830 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13161 AN: 67992

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.192 Hom.: 1816

Bravo AF: 0.192

Asia WGS AF: 0.101 AC: 353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1487562; hg19: chr10-45928822;