rs12264801

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ALOX5	NM_000698.5	c.555-4745G>A		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.555-4745G>A		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.555-4745G>A		intron_variant		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

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.445

Alfa AF: 0.453 Hom.: 2039

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12264801; hg19: chr10-45914744; COSMIC: COSV65552401; COSMIC: COSV65552401;