10-45374300-C-T

Variant names:

• chr10-45374300-C-T
• rs4987105
• NM_000698.5:c.21C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001320862.2(ALOX5):​c.-453C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,509,264 control chromosomes in the GnomAD database, including 20,054 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 0.16 (2056 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17998 hom.)
• Consequence: ALOX5 NM_001320862.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 38 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320862.2. 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.21C>T	p.Thr7Thr	synonymous	Exon 1 of 14	NP_000689.1	P09917-1
	ALOX5	NM_001320862.2		c.-453C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001307791.1
	ALOX5	NM_001320861.2		c.21C>T	p.Thr7Thr	synonymous	Exon 1 of 14	NP_001307790.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.21C>T	p.Thr7Thr	synonymous	Exon 1 of 14	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.21C>T	p.Thr7Thr	synonymous	Exon 1 of 13	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.21C>T	p.Thr7Thr	synonymous	Exon 1 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24505 AN: 151938 Hom.: 2052 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.152 AC: 17706 AN: 116540 AF XY: 0.156

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0887

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.160 AC: 217071 AN: 1357218 Hom.: 17998 Cov.: 32 AF XY: 0.161 AC XY: 107486 AN XY: 669530

African (AFR) AF: 0.151 AC: 4181 AN: 27612

American (AMR) AF: 0.0914 AC: 2769 AN: 30290

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3848 AN: 23722

East Asian (EAS) AF: 0.178 AC: 5399 AN: 30320

South Asian (SAS) AF: 0.188 AC: 14127 AN: 75206

European-Finnish (FIN) AF: 0.186 AC: 8753 AN: 46944

Middle Eastern (MID) AF: 0.110 AC: 611 AN: 5552

European-Non Finnish (NFE) AF: 0.159 AC: 168389 AN: 1061608

Other (OTH) AF: 0.161 AC: 8994 AN: 55964

GnomAD4 genome AF: 0.161 AC: 24529 AN: 152046 Hom.: 2056 Cov.: 33 AF XY: 0.163 AC XY: 12108 AN XY: 74312

African (AFR) AF: 0.155 AC: 6437 AN: 41498

American (AMR) AF: 0.131 AC: 2009 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3466

East Asian (EAS) AF: 0.181 AC: 924 AN: 5116

South Asian (SAS) AF: 0.189 AC: 911 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2055 AN: 10602

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11042 AN: 67934

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.132 Hom.: 604

Bravo AF: 0.156

Asia WGS AF: 0.152 AC: 525 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-1.3
PromoterAI		0.0059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=99/1	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: rs4987105; hg19: chr10-45869748; COSMIC: COSV65552228;