10-45396036-A-G

Variant names:

• chr10-45396036-A-G
• rs2029253
• NM_000698.5:c.431+100A>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.431+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,229,478 control chromosomes in the GnomAD database, including 99,524 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 0.38 (11515 hom., cov: 33)
  • Exomes 𝑓: 0.40 (88009 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 32 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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.431+100A>G		intron	N/A	NP_000689.1
	ALOX5	NM_001320861.2		c.431+100A>G		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.431+100A>G		intron	N/A	NP_001243082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.431+100A>G		intron	N/A	ENSP00000363512.2
	ALOX5	ENST00000542434.5	TSL:1	c.431+100A>G		intron	N/A	ENSP00000437634.1
	ALOX5	ENST00000851643.1		c.431+100A>G		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57485 AN: 152022 Hom.: 11509 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.397 AC: 428093 AN: 1077338 Hom.: 88009 AF XY: 0.394 AC XY: 212985 AN XY: 540154

African (AFR) AF: 0.259 AC: 6361 AN: 24522

American (AMR) AF: 0.543 AC: 17114 AN: 31496

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 7662 AN: 21346

East Asian (EAS) AF: 0.598 AC: 20033 AN: 33520

South Asian (SAS) AF: 0.328 AC: 22557 AN: 68744

European-Finnish (FIN) AF: 0.467 AC: 22606 AN: 48408

Middle Eastern (MID) AF: 0.430 AC: 2133 AN: 4956

European-Non Finnish (NFE) AF: 0.390 AC: 311005 AN: 797398

Other (OTH) AF: 0.397 AC: 18622 AN: 46948

GnomAD4 genome AF: 0.378 AC: 57513 AN: 152140 Hom.: 11515 Cov.: 33 AF XY: 0.385 AC XY: 28655 AN XY: 74374

African (AFR) AF: 0.270 AC: 11193 AN: 41498

American (AMR) AF: 0.478 AC: 7305 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.607 AC: 3142 AN: 5180

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4818

European-Finnish (FIN) AF: 0.475 AC: 5023 AN: 10584

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26620 AN: 67984

Other (OTH) AF: 0.394 AC: 831 AN: 2110

Alfa AF: 0.390 Hom.: 39968

Bravo AF: 0.381

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.49
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2029253; hg19: chr10-45891484;