rs2291427

Positions:

• chr10-45440776-A-G
• chr10-45440776-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.1185+143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 904,478 control chromosomes in the GnomAD database, including 219,159 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 0.73 (40877 hom., cov: 32)
  • Exomes 𝑓: 0.69 (178282 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.1185+143A>G		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.1185+143A>G		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.1185+143A>G		intron_variant		1
ALOX5	ENST00000475300.1	n.204+143A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110871 AN: 152002 Hom.: 40822 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.685 AC: 515656 AN: 752358 Hom.: 178282 AF XY: 0.680 AC XY: 259910 AN XY: 382164

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.601

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.698

GnomAD4 genome AF: 0.730 AC: 110988 AN: 152120 Hom.: 40877 Cov.: 32 AF XY: 0.727 AC XY: 54077 AN XY: 74366

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.720

Alfa AF: 0.694 Hom.: 38064

Bravo AF: 0.736

Asia WGS AF: 0.663 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.73

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: rs2291427; hg19: chr10-45936224;