rs7894352

Variant names:

• chr10-45407464-A-G
• rs7894352
• NM_000698.5:c.432-4727A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-45407464-A-G
• chr10-45407464-A-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.432-4727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 151,664 control chromosomes in the GnomAD database, including 51,749 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 0.82 (51749 hom., cov: 29)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-4727A>G		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.432-4727A>G		intron_variant	Intron 3 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.432-4727A>G		intron_variant	Intron 3 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 124848 AN: 151550 Hom.: 51701 Cov.: 29

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.824 AC: 124949 AN: 151664 Hom.: 51749 Cov.: 29 AF XY: 0.824 AC XY: 61025 AN XY: 74100

African (AFR) AF: 0.886 AC: 36584 AN: 41286

American (AMR) AF: 0.839 AC: 12812 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2503 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4422 AN: 5150

South Asian (SAS) AF: 0.681 AC: 3273 AN: 4808

European-Finnish (FIN) AF: 0.856 AC: 8946 AN: 10450

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.791 AC: 53725 AN: 67928

Other (OTH) AF: 0.801 AC: 1686 AN: 2104

Alfa AF: 0.805 Hom.: 49948

Bravo AF: 0.829

Asia WGS AF: 0.776 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.11
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: rs7894352; hg19: chr10-45902912;