rs3740107

chr10-45428322-A-G

Variant summary

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

The NM_000698.5(ALOX5):c.835-296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 468,210 control chromosomes in the GnomAD database, including 131,799 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 0.76 (43765 hom., cov: 31)
  • Exomes 𝑓: 0.74 (88034 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.835-296A>G		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.835-296A>G		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.835-296A>G		intron_variant		1
ALOX5	ENST00000483623.2	n.238-39A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115032 AN: 151892 Hom.: 43723 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.743 AC: 235013 AN: 316200 Hom.: 88034 Cov.: 3 AF XY: 0.737 AC XY: 120137 AN XY: 162970

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.785

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.751

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.757 AC: 115129 AN: 152010 Hom.: 43765 Cov.: 31 AF XY: 0.756 AC XY: 56162 AN XY: 74282

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.744

Alfa AF: 0.764 Hom.: 12600

Bravo AF: 0.757

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.4
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs3740107; hg19: chr10-45923770;