rs2115819

Positions:

• chr10-45405641-A-G
• chr10-45405641-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.432-6550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,962 control chromosomes in the GnomAD database, including 14,593 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 0.42 (14593 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-6550A>G		intron_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.432-6550A>G		intron_variant		1	NM_000698.5	ENSP00000363512	P1
ALOX5	ENST00000542434.5	c.432-6550A>G		intron_variant		1		ENSP00000437634

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64199 AN: 151848 Hom.: 14588 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.423 AC: 64228 AN: 151962 Hom.: 14593 Cov.: 32 AF XY: 0.432 AC XY: 32109 AN XY: 74268

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.438

Alfa AF: 0.442 Hom.: 6859

Bravo AF: 0.422

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.67

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: rs2115819; hg19: chr10-45901089;