rs1369214

Variant names:

• chr10-45405281-G-A
• rs1369214
• NM_000698.5:c.432-6910G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-45405281-G-A
• chr10-45405281-G-C
• chr10-45405281-G-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.432-6910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,932 control chromosomes in the GnomAD database, including 20,488 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 0.51 (20488 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 14 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-6910G>A		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.432-6910G>A		intron_variant	Intron 3 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.432-6910G>A		intron_variant	Intron 3 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77711 AN: 151812 Hom.: 20475 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.512 AC: 77765 AN: 151932 Hom.: 20488 Cov.: 32 AF XY: 0.518 AC XY: 38450 AN XY: 74212

African (AFR) AF: 0.557 AC: 23071 AN: 41396

American (AMR) AF: 0.574 AC: 8776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4415 AN: 5166

South Asian (SAS) AF: 0.519 AC: 2503 AN: 4820

European-Finnish (FIN) AF: 0.525 AC: 5526 AN: 10522

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30314 AN: 67952

Other (OTH) AF: 0.509 AC: 1077 AN: 2116

Alfa AF: 0.480 Hom.: 21188

Bravo AF: 0.523

Asia WGS AF: 0.662 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.62
PhyloP100		-0.63
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: rs1369214; hg19: chr10-45900729;