10-45428575-G-A

Variant names:

• chr10-45428575-G-A
• rs1565096
• NM_000698.5:c.835-43G>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.835-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,609,578 control chromosomes in the GnomAD database, including 470,038 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 0.80 (49522 hom., cov: 31)
  • Exomes 𝑓: 0.76 (420516 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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.835-43G>A		intron	N/A	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.835-43G>A		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.835-43G>A		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.835-43G>A		intron	N/A	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.835-43G>A		intron	N/A	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.828G>A	p.Pro276Pro	synonymous	Exon 7 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122026 AN: 152000 Hom.: 49460 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.788

GnomAD2 exomes AF: 0.767 AC: 189739 AN: 247290 AF XY: 0.756

Gnomad AFR exome AF: 0.909

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.819

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.758 AC: 1104843 AN: 1457460 Hom.: 420516 Cov.: 44 AF XY: 0.753 AC XY: 545692 AN XY: 724564

African (AFR) AF: 0.910 AC: 30420 AN: 33414

American (AMR) AF: 0.832 AC: 37115 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 18110 AN: 25926

East Asian (EAS) AF: 0.793 AC: 31417 AN: 39630

South Asian (SAS) AF: 0.643 AC: 55316 AN: 85968

European-Finnish (FIN) AF: 0.800 AC: 42543 AN: 53182

Middle Eastern (MID) AF: 0.749 AC: 4036 AN: 5388

European-Non Finnish (NFE) AF: 0.757 AC: 839893 AN: 1109178

Other (OTH) AF: 0.764 AC: 45993 AN: 60190

GnomAD4 genome AF: 0.803 AC: 122146 AN: 152118 Hom.: 49522 Cov.: 31 AF XY: 0.801 AC XY: 59564 AN XY: 74352

African (AFR) AF: 0.908 AC: 37727 AN: 41552

American (AMR) AF: 0.814 AC: 12444 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2376 AN: 3468

East Asian (EAS) AF: 0.804 AC: 4131 AN: 5138

South Asian (SAS) AF: 0.636 AC: 3053 AN: 4802

European-Finnish (FIN) AF: 0.805 AC: 8515 AN: 10572

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51319 AN: 67976

Other (OTH) AF: 0.786 AC: 1661 AN: 2114

Alfa AF: 0.769 Hom.: 66790

Bravo AF: 0.810

Asia WGS AF: 0.744 AC: 2589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.015
DANN	Benign	0.75
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1565096; hg19: chr10-45924023;