chr10-45380532-C-T

Variant names:

• chr10-45380532-C-T
• rs3824613
• NM_000698.5:c.151-1951C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):​c.151-1951C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,214 control chromosomes in the GnomAD database, including 2,140 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 (2140 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.151-1951C>T		intron_variant	Intron 1 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.151-1951C>T		intron_variant	Intron 1 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.151-1951C>T		intron_variant	Intron 1 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25071 AN: 152096 Hom.: 2133 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.165 AC: 25109 AN: 152214 Hom.: 2140 Cov.: 33 AF XY: 0.167 AC XY: 12400 AN XY: 74414

African (AFR) AF: 0.169 AC: 7001 AN: 41542

American (AMR) AF: 0.132 AC: 2026 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3470

East Asian (EAS) AF: 0.183 AC: 946 AN: 5164

South Asian (SAS) AF: 0.189 AC: 912 AN: 4832

European-Finnish (FIN) AF: 0.195 AC: 2061 AN: 10592

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10996 AN: 67994

Other (OTH) AF: 0.163 AC: 344 AN: 2116

Alfa AF: 0.157 Hom.: 747

Bravo AF: 0.159

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.54
PhyloP100		-1.5
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: rs3824613; hg19: chr10-45875980; COSMIC: COSV65552855;