NM_000698.5:c.432-185G>C

Variant names:

• chr10-45412006-G-C
• rs10900215
• NM_000698.5:c.432-185G>C

Variant summary

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

The NM_000698.5(ALOX5):​c.432-185G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,158 control chromosomes in the GnomAD database, including 2,882 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 0.18 (2882 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.432-185G>C		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.432-185G>C		intron_variant	Intron 3 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.432-185G>C		intron_variant	Intron 3 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27397 AN: 152040 Hom.: 2868 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.180 AC: 27452 AN: 152158 Hom.: 2882 Cov.: 32 AF XY: 0.182 AC XY: 13523 AN XY: 74404

African (AFR) AF: 0.265 AC: 10996 AN: 41496

American (AMR) AF: 0.118 AC: 1798 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3462

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0857 AC: 414 AN: 4830

European-Finnish (FIN) AF: 0.226 AC: 2396 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10873 AN: 67988

Other (OTH) AF: 0.153 AC: 323 AN: 2108

Alfa AF: 0.0834 Hom.: 131

Bravo AF: 0.173

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.074
DANN	Benign	0.44
PhyloP100		-2.5
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: rs10900215; hg19: chr10-45907454;