chr10-45409266-G-T

Variant names:

• chr10-45409266-G-T
• rs10900213
• NM_000698.5:c.432-2925G>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.432-2925G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,024 control chromosomes in the GnomAD database, including 21,729 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 0.53 (21729 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-2925G>T		intron_variant	Intron 3 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.432-2925G>T		intron_variant	Intron 3 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.432-2925G>T		intron_variant	Intron 3 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80135 AN: 151906 Hom.: 21705 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.528 AC: 80197 AN: 152024 Hom.: 21729 Cov.: 33 AF XY: 0.537 AC XY: 39890 AN XY: 74306

African (AFR) AF: 0.422 AC: 17489 AN: 41402

American (AMR) AF: 0.580 AC: 8876 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3462

East Asian (EAS) AF: 0.616 AC: 3187 AN: 5176

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4814

European-Finnish (FIN) AF: 0.707 AC: 7481 AN: 10574

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37572 AN: 67982

Other (OTH) AF: 0.527 AC: 1112 AN: 2112

Alfa AF: 0.532 Hom.: 29826

Bravo AF: 0.517

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.52
PhyloP100		-0.64
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: rs10900213; hg19: chr10-45904714;