10-45421644-A-G

Variant names:

• chr10-45421644-A-G
• rs892691
• NM_000698.5:c.555-2397A>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.555-2397A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,216 control chromosomes in the GnomAD database, including 39,184 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 0.71 (39184 hom., cov: 34)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.555-2397A>G		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.555-2397A>G		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.555-2397A>G		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108663 AN: 152098 Hom.: 39162 Cov.: 34

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.714 AC: 108736 AN: 152216 Hom.: 39184 Cov.: 34 AF XY: 0.716 AC XY: 53296 AN XY: 74426

African (AFR) AF: 0.666 AC: 27629 AN: 41516

American (AMR) AF: 0.752 AC: 11511 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4514 AN: 5182

South Asian (SAS) AF: 0.637 AC: 3075 AN: 4824

European-Finnish (FIN) AF: 0.789 AC: 8365 AN: 10606

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49177 AN: 67998

Other (OTH) AF: 0.690 AC: 1457 AN: 2112

Alfa AF: 0.731 Hom.: 6664

Bravo AF: 0.711

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.63
PhyloP100		-1.2
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: rs892691; hg19: chr10-45917092;