rs1059696

Variant names:

• chr10-45438989-G-A
• rs1059696
• NM_000698.5:c.982-1441G>A

Variant summary

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

The NM_000698.5(ALOX5):​c.982-1441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,024 control chromosomes in the GnomAD database, including 2,554 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 0.18 (2554 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.982-1441G>A		intron_variant	Intron 7 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.982-1441G>A		intron_variant	Intron 7 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.982-1441G>A		intron_variant	Intron 7 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27184 AN: 151906 Hom.: 2556 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.179 AC: 27195 AN: 152024 Hom.: 2554 Cov.: 32 AF XY: 0.181 AC XY: 13452 AN XY: 74304

African (AFR) AF: 0.204 AC: 8435 AN: 41422

American (AMR) AF: 0.127 AC: 1941 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 460 AN: 3472

East Asian (EAS) AF: 0.0461 AC: 238 AN: 5168

South Asian (SAS) AF: 0.176 AC: 849 AN: 4818

European-Finnish (FIN) AF: 0.241 AC: 2542 AN: 10542

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12166 AN: 67988

Other (OTH) AF: 0.168 AC: 355 AN: 2116

Alfa AF: 0.175 Hom.: 1281

Bravo AF: 0.167

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.39
PhyloP100		-1.1
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: rs1059696; hg19: chr10-45934437;