rs7090328

Variant names:

• chr10-45422628-A-G
• rs7090328
• NM_000698.5:c.555-1413A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-45422628-A-G
• chr10-45422628-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.555-1413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,172 control chromosomes in the GnomAD database, including 46,091 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 0.77 (46091 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.555-1413A>G		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.555-1413A>G		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.555-1413A>G		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117635 AN: 152054 Hom.: 46051 Cov.: 33

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.774 AC: 117730 AN: 152172 Hom.: 46091 Cov.: 33 AF XY: 0.773 AC XY: 57539 AN XY: 74388

African (AFR) AF: 0.870 AC: 36134 AN: 41520

American (AMR) AF: 0.781 AC: 11945 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1991 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4492 AN: 5176

South Asian (SAS) AF: 0.653 AC: 3144 AN: 4818

European-Finnish (FIN) AF: 0.788 AC: 8347 AN: 10590

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49216 AN: 67978

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.721 Hom.: 20976

Bravo AF: 0.780

Asia WGS AF: 0.770 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.039
DANN	Benign	0.38
PhyloP100		-1.0
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: rs7090328; hg19: chr10-45918076;