chr10-45382602-G-A

Variant names:

• chr10-45382602-G-A
• rs2228064
• NM_000698.5:c.270G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000698.5(ALOX5):​c.270G>A​(p.Thr90Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,990 control chromosomes in the GnomAD database, including 3,665 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 0.091 (1862 hom., cov: 33)
  • Exomes 𝑓: 0.015 (1803 hom.)
• Consequence: ALOX5 NM_000698.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 36 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 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.270G>A	p.Thr90Thr	synonymous	Exon 2 of 14	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.270G>A	p.Thr90Thr	synonymous	Exon 2 of 14	NP_001307790.1
	ALOX5	NM_001256153.3		c.270G>A	p.Thr90Thr	synonymous	Exon 2 of 14	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.270G>A	p.Thr90Thr	synonymous	Exon 2 of 14	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.270G>A	p.Thr90Thr	synonymous	Exon 2 of 13	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.270G>A	p.Thr90Thr	synonymous	Exon 2 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13870 AN: 152086 Hom.: 1860 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.0726

GnomAD2 exomes AF: 0.0362 AC: 9083 AN: 251184 AF XY: 0.0287

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.0623

Gnomad FIN exome AF: 0.0119

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0150 AC: 21935 AN: 1461786 Hom.: 1803 Cov.: 33 AF XY: 0.0138 AC XY: 10019 AN XY: 727196

African (AFR) AF: 0.300 AC: 10043 AN: 33474

American (AMR) AF: 0.0499 AC: 2231 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00321 AC: 84 AN: 26136

East Asian (EAS) AF: 0.0522 AC: 2073 AN: 39700

South Asian (SAS) AF: 0.0150 AC: 1297 AN: 86254

European-Finnish (FIN) AF: 0.0131 AC: 701 AN: 53352

Middle Eastern (MID) AF: 0.0168 AC: 97 AN: 5768

European-Non Finnish (NFE) AF: 0.00323 AC: 3587 AN: 1112000

Other (OTH) AF: 0.0302 AC: 1822 AN: 60390

GnomAD4 genome AF: 0.0913 AC: 13898 AN: 152204 Hom.: 1862 Cov.: 33 AF XY: 0.0880 AC XY: 6552 AN XY: 74416

African (AFR) AF: 0.290 AC: 12043 AN: 41476

American (AMR) AF: 0.0555 AC: 849 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0693 AC: 359 AN: 5184

South Asian (SAS) AF: 0.0192 AC: 93 AN: 4832

European-Finnish (FIN) AF: 0.00970 AC: 103 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00412 AC: 280 AN: 68014

Other (OTH) AF: 0.0718 AC: 152 AN: 2116

Alfa AF: 0.0306 Hom.: 2123

Bravo AF: 0.103

Asia WGS AF: 0.0710 AC: 246 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-2.6
Mutation Taster		=98/2	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: rs2228064; hg19: chr10-45878050; COSMIC: COSV65552512;