rs2288619

Positions:

• chr10-45444370-C-T

Variant summary

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

The NM_000698.5(ALOX5):​c.1845+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,448,798 control chromosomes in the GnomAD database, including 4,174 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 0.090 (827 hom., cov: 33)
  • Exomes 𝑓: 0.069 (3347 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.1845+84C>T		intron_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.1845+84C>T		intron_variant		1	NM_000698.5	ENSP00000363512	P1
ALOX5	ENST00000542434.5	c.1674+542C>T		intron_variant		1		ENSP00000437634

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13738 AN: 152182 Hom.: 821 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0223

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0686 AC: 88903 AN: 1296498 Hom.: 3347 Cov.: 26 AF XY: 0.0671 AC XY: 42242 AN XY: 629736

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0440

Gnomad4 ASJ exome AF: 0.0386

Gnomad4 EAS exome AF: 0.0888

Gnomad4 SAS exome AF: 0.0236

Gnomad4 FIN exome AF: 0.0763

Gnomad4 NFE exome AF: 0.0692

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.0903 AC: 13759 AN: 152300 Hom.: 827 Cov.: 33 AF XY: 0.0893 AC XY: 6649 AN XY: 74468

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0400

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.0221

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0850 Hom.: 97

Bravo AF: 0.0940

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.65

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: rs2288619; hg19: chr10-45939818;