rs2029253

Positions:

• chr10-45396036-A-G
• chr10-45396036-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):​c.431+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,229,478 control chromosomes in the GnomAD database, including 99,524 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 0.38 (11515 hom., cov: 33)
  • Exomes 𝑓: 0.40 (88009 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.431+100A>G		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.431+100A>G		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.431+100A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57485 AN: 152022 Hom.: 11509 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.397 AC: 428093 AN: 1077338 Hom.: 88009 AF XY: 0.394 AC XY: 212985 AN XY: 540154

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.378 AC: 57513 AN: 152140 Hom.: 11515 Cov.: 33 AF XY: 0.385 AC XY: 28655 AN XY: 74374

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.394

Alfa AF: 0.391 Hom.: 12276

Bravo AF: 0.381

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2029253; hg19: chr10-45891484;