rs1565096

Positions:

• chr10-45428575-G-A
• chr10-45428575-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.835-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,609,578 control chromosomes in the GnomAD database, including 470,038 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 0.80 (49522 hom., cov: 31)
  • Exomes 𝑓: 0.76 (420516 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.835-43G>A		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.835-43G>A		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.835-43G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122026 AN: 152000 Hom.: 49460 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.788

GnomAD3 exomes AF: 0.767 AC: 189739 AN: 247290 Hom.: 73460 AF XY: 0.756 AC XY: 101221 AN XY: 133882

Gnomad AFR exome AF: 0.909

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.819

Gnomad SAS exome AF: 0.641

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.758 AC: 1104843 AN: 1457460 Hom.: 420516 Cov.: 44 AF XY: 0.753 AC XY: 545692 AN XY: 724564

Gnomad4 AFR exome AF: 0.910

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.699

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.764

GnomAD4 genome AF: 0.803 AC: 122146 AN: 152118 Hom.: 49522 Cov.: 31 AF XY: 0.801 AC XY: 59564 AN XY: 74352

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.786

Alfa AF: 0.765 Hom.: 7203

Bravo AF: 0.810

Asia WGS AF: 0.744 AC: 2589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.015
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1565096; hg19: chr10-45924023;