NM_000698.5:c.432-5102G>T

Variant names:

• chr10-45407089-G-T
• rs11239516
• NM_000698.5:c.432-5102G>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.432-5102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,016 control chromosomes in the GnomAD database, including 1,915 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 0.15 (1915 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-5102G>T		intron_variant	Intron 3 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.432-5102G>T		intron_variant	Intron 3 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.432-5102G>T		intron_variant	Intron 3 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22894 AN: 151898 Hom.: 1910 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152016 Hom.: 1915 Cov.: 32 AF XY: 0.153 AC XY: 11338 AN XY: 74314

African (AFR) AF: 0.163 AC: 6761 AN: 41450

American (AMR) AF: 0.105 AC: 1596 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.0843 AC: 406 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2395 AN: 10558

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10843 AN: 67970

Other (OTH) AF: 0.131 AC: 276 AN: 2108

Alfa AF: 0.0797 Hom.: 128

Bravo AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.71
PhyloP100		-0.97
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: rs11239516; hg19: chr10-45902537;