rs2228064

Positions:

• chr10-45382602-G-A
• chr10-45382602-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000698.5(ALOX5):​c.270G>A​(p.Thr90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,990 control chromosomes in the GnomAD database, including 3,665 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 0.091 (1862 hom., cov: 33)
  • Exomes 𝑓: 0.015 (1803 hom.)
• Consequence: ALOX5 NM_000698.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.270G>A	p.Thr90=	synonymous_variant	2/14	ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.270G>A	p.Thr90=	synonymous_variant	2/14	1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.270G>A	p.Thr90=	synonymous_variant	2/13	1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13870 AN: 152086 Hom.: 1860 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.0726

GnomAD3 exomes AF: 0.0362 AC: 9083 AN: 251184 Hom.: 797 AF XY: 0.0287 AC XY: 3904 AN XY: 135820

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.0623

Gnomad SAS exome AF: 0.0143

Gnomad FIN exome AF: 0.0119

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0150 AC: 21935 AN: 1461786 Hom.: 1803 Cov.: 33 AF XY: 0.0138 AC XY: 10019 AN XY: 727196

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.00321

Gnomad4 EAS exome AF: 0.0522

Gnomad4 SAS exome AF: 0.0150

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.00323

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.0913 AC: 13898 AN: 152204 Hom.: 1862 Cov.: 33 AF XY: 0.0880 AC XY: 6552 AN XY: 74416

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0555

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0693

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.00412

Gnomad4 OTH AF: 0.0718

Alfa AF: 0.0212 Hom.: 577

Bravo AF: 0.103

Asia WGS AF: 0.0710 AC: 246 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.8
DANN	Benign	0.79

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: rs2228064; hg19: chr10-45878050; COSMIC: COSV65552512;