rs3740107

Variant names:

• chr10-45428322-A-G
• rs3740107
• NM_000698.5:c.835-296A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.835-296A>G		intron_variant	Intron 6 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.835-296A>G		intron_variant	Intron 6 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.835-296A>G		intron_variant	Intron 6 of 12	1		ENSP00000437634.1
ALOX5	ENST00000483623.2	n.238-39A>G		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.762 AC: 7529 AN: 9880

American (AMR) AF: 0.785 AC: 9511 AN: 12122

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 7316 AN: 10536

East Asian (EAS) AF: 0.751 AC: 18159 AN: 24182

South Asian (SAS) AF: 0.611 AC: 12924 AN: 21138

European-Finnish (FIN) AF: 0.800 AC: 17596 AN: 22004

Middle Eastern (MID) AF: 0.674 AC: 1013 AN: 1502

European-Non Finnish (NFE) AF: 0.749 AC: 146249 AN: 195180

Other (OTH) AF: 0.749 AC: 14716 AN: 19656

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

African (AFR) AF: 0.776 AC: 32163 AN: 41446

American (AMR) AF: 0.777 AC: 11883 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2357 AN: 3472

East Asian (EAS) AF: 0.749 AC: 3844 AN: 5130

South Asian (SAS) AF: 0.608 AC: 2926 AN: 4810

European-Finnish (FIN) AF: 0.805 AC: 8500 AN: 10562

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50973 AN: 67980

Other (OTH) AF: 0.744 AC: 1572 AN: 2112

Alfa AF: 0.758 Hom.: 19885

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
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3740107; hg19: chr10-45923770;