10-45426534-A-G

Variant names:

• chr10-45426534-A-G
• rs3780906
• NM_000698.5:c.834+1402A>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.834+1402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,198 control chromosomes in the GnomAD database, including 38,179 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 (38179 hom., cov: 34)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 23 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 = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000698.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	NM_000698.5	MANE Select	c.834+1402A>G		intron	N/A	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.834+1402A>G		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.834+1402A>G		intron	N/A	NP_001243082.1	P09917-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.834+1402A>G		intron	N/A	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.834+1402A>G		intron	N/A	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.811+1402A>G		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107242 AN: 152078 Hom.: 38149 Cov.: 34

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.705 AC: 107312 AN: 152198 Hom.: 38179 Cov.: 34 AF XY: 0.705 AC XY: 52443 AN XY: 74414

African (AFR) AF: 0.639 AC: 26515 AN: 41506

American (AMR) AF: 0.746 AC: 11405 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2241 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4093 AN: 5178

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4826

European-Finnish (FIN) AF: 0.786 AC: 8329 AN: 10594

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49730 AN: 68004

Other (OTH) AF: 0.697 AC: 1474 AN: 2114

Alfa AF: 0.721 Hom.: 32236

Bravo AF: 0.702

Asia WGS AF: 0.663 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		-0.37
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: rs3780906; hg19: chr10-45921982;