rs7918542

Variant names:

• chr10-45400803-A-G
• rs7918542
• NM_000698.5:c.431+4867A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-45400803-A-G
• chr10-45400803-A-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.431+4867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,022 control chromosomes in the GnomAD database, including 4,075 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 0.23 (4075 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000698.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	NM_000698.5	MANE Select	c.431+4867A>G		intron	N/A	NP_000689.1
	ALOX5	NM_001320861.2		c.431+4867A>G		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.431+4867A>G		intron	N/A	NP_001243082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.431+4867A>G		intron	N/A	ENSP00000363512.2
	ALOX5	ENST00000542434.5	TSL:1	c.431+4867A>G		intron	N/A	ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34556 AN: 151902 Hom.: 4066 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.228 AC: 34601 AN: 152022 Hom.: 4075 Cov.: 32 AF XY: 0.231 AC XY: 17141 AN XY: 74288

African (AFR) AF: 0.260 AC: 10772 AN: 41450

American (AMR) AF: 0.170 AC: 2605 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3466

East Asian (EAS) AF: 0.180 AC: 934 AN: 5176

South Asian (SAS) AF: 0.257 AC: 1235 AN: 4812

European-Finnish (FIN) AF: 0.267 AC: 2820 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14844 AN: 67960

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.217 Hom.: 502

Bravo AF: 0.218

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7918542; hg19: chr10-45896251;