chr10-45428080-C-A

Variant names:

• chr10-45428080-C-A
• rs2279435
• NM_000698.5:c.835-538C>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.835-538C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.58 (24652 hom., cov: 19)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.835-538C>A		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.835-538C>A		intron_variant	Intron 6 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.835-538C>A		intron_variant	Intron 6 of 12	1		ENSP00000437634.1
ALOX5	ENST00000483623.2	n.238-281C>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 82354 AN: 140982 Hom.: 24619 Cov.: 19

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.610

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.584 AC: 82429 AN: 141094 Hom.: 24652 Cov.: 19 AF XY: 0.579 AC XY: 39515 AN XY: 68240

African (AFR) AF: 0.609 AC: 22641 AN: 37184

American (AMR) AF: 0.661 AC: 9246 AN: 13996

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1833 AN: 3378

East Asian (EAS) AF: 0.759 AC: 3518 AN: 4632

South Asian (SAS) AF: 0.423 AC: 1841 AN: 4354

European-Finnish (FIN) AF: 0.544 AC: 5035 AN: 9248

Middle Eastern (MID) AF: 0.621 AC: 174 AN: 280

European-Non Finnish (NFE) AF: 0.560 AC: 36562 AN: 65252

Other (OTH) AF: 0.584 AC: 1116 AN: 1912

Alfa AF: 0.649 Hom.: 8988

Bravo AF: 0.608

Asia WGS AF: 0.619 AC: 2144 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.59
PhyloP100		-2.3
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: rs2279435; hg19: chr10-45923528;