rs2279435

chr10-45428080-C-Achr10-45428080-C-G

Variant summary

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

The NM_000698.5(ALOX5):c.835-538C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 141,094 control chromosomes in the GnomAD database, including 24,652 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 0.58 (24652 hom., cov: 19)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.835-538C>A		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.835-538C>A		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.835-538C>A		intron_variant		1
ALOX5	ENST00000483623.2	n.238-281C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 82354 AN: 140982 Hom.: 24619 Cov.: 19

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.584 AC: 82429 AN: 141094 Hom.: 24652 Cov.: 19 AF XY: 0.579 AC XY: 39515 AN XY: 68240

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.584

Alfa AF: 0.641 Hom.: 7961

Bravo AF: 0.608

Asia WGS AF: 0.619 AC: 2144 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.39
Dann	Benign	0.59

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: rs2279435; hg19: chr10-45923528;