rs2291427

Variant names:

• chr10-45440776-A-G
• rs2291427
• NM_000698.5:c.1185+143A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-45440776-A-G
• chr10-45440776-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):​c.1185+143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 904,478 control chromosomes in the GnomAD database, including 219,159 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 0.73 (40877 hom., cov: 32)
  • Exomes 𝑓: 0.69 (178282 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.1185+143A>G		intron_variant	Intron 8 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.1185+143A>G		intron_variant	Intron 8 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.1185+143A>G		intron_variant	Intron 8 of 12	1		ENSP00000437634.1
ALOX5	ENST00000475300.1	n.204+143A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110871 AN: 152002 Hom.: 40822 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.685 AC: 515656 AN: 752358 Hom.: 178282 AF XY: 0.680 AC XY: 259910 AN XY: 382164

African (AFR) AF: 0.822 AC: 15145 AN: 18430

American (AMR) AF: 0.762 AC: 17715 AN: 23250

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 10702 AN: 16268

East Asian (EAS) AF: 0.646 AC: 21061 AN: 32604

South Asian (SAS) AF: 0.601 AC: 32242 AN: 53618

European-Finnish (FIN) AF: 0.719 AC: 23336 AN: 32434

Middle Eastern (MID) AF: 0.684 AC: 1777 AN: 2598

European-Non Finnish (NFE) AF: 0.686 AC: 368325 AN: 536820

Other (OTH) AF: 0.698 AC: 25353 AN: 36336

GnomAD4 genome AF: 0.730 AC: 110988 AN: 152120 Hom.: 40877 Cov.: 32 AF XY: 0.727 AC XY: 54077 AN XY: 74366

African (AFR) AF: 0.826 AC: 34298 AN: 41498

American (AMR) AF: 0.747 AC: 11424 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3499 AN: 5168

South Asian (SAS) AF: 0.595 AC: 2868 AN: 4820

European-Finnish (FIN) AF: 0.734 AC: 7764 AN: 10584

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46549 AN: 67978

Other (OTH) AF: 0.720 AC: 1520 AN: 2110

Alfa AF: 0.700 Hom.: 52243

Bravo AF: 0.736

Asia WGS AF: 0.663 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291427; hg19: chr10-45936224;