rs3780909

Variant names:

• chr10-45429767-T-A
• rs3780909
• NM_000698.5:c.981+1003T>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.981+1003T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,950 control chromosomes in the GnomAD database, including 19,614 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 0.50 (19614 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 9 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.981+1003T>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.981+1003T>A		intron_variant	Intron 7 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.981+1003T>A		intron_variant	Intron 7 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76560 AN: 151832 Hom.: 19588 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.504 AC: 76633 AN: 151950 Hom.: 19614 Cov.: 32 AF XY: 0.502 AC XY: 37322 AN XY: 74298

African (AFR) AF: 0.476 AC: 19714 AN: 41428

American (AMR) AF: 0.599 AC: 9149 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3468

East Asian (EAS) AF: 0.650 AC: 3353 AN: 5158

South Asian (SAS) AF: 0.417 AC: 2007 AN: 4810

European-Finnish (FIN) AF: 0.494 AC: 5217 AN: 10566

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33736 AN: 67926

Other (OTH) AF: 0.518 AC: 1095 AN: 2114

Alfa AF: 0.511 Hom.: 2500

Bravo AF: 0.515

Asia WGS AF: 0.517 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.30
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: rs3780909; hg19: chr10-45925215;