rs12264801

Variant names:

• chr10-45419296-G-A
• rs12264801
• NM_000698.5:c.555-4745G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-45419296-G-A
• chr10-45419296-G-C

Variant summary

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

The NM_000698.5(ALOX5):​c.555-4745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,344 control chromosomes in the GnomAD database, including 15,729 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 0.45 (15729 hom., cov: 34)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.555-4745G>A		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.555-4745G>A		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.555-4745G>A		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68407 AN: 151230 Hom.: 15729 Cov.: 34

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.452 AC: 68438 AN: 151344 Hom.: 15729 Cov.: 34 AF XY: 0.459 AC XY: 33941 AN XY: 73966

African (AFR) AF: 0.401 AC: 16481 AN: 41102

American (AMR) AF: 0.500 AC: 7618 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3466

East Asian (EAS) AF: 0.448 AC: 2277 AN: 5080

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4816

European-Finnish (FIN) AF: 0.539 AC: 5691 AN: 10566

Middle Eastern (MID) AF: 0.383 AC: 111 AN: 290

European-Non Finnish (NFE) AF: 0.461 AC: 31240 AN: 67770

Other (OTH) AF: 0.445 AC: 940 AN: 2110

Alfa AF: 0.425 Hom.: 3155

Bravo AF: 0.446

Asia WGS AF: 0.474 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.91
PhyloP100		-1.0
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: rs12264801; hg19: chr10-45914744; COSMIC: COSV65552401; COSMIC: COSV65552401;