10-45435337-T-C

Variant names:

• chr10-45435337-T-C
• rs4540799
• NM_000698.5:c.982-5093T>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.982-5093T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,554 control chromosomes in the GnomAD database, including 43,743 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 0.76 (43743 hom., cov: 29)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	NM_000698.5	MANE Select	c.982-5093T>C		intron	N/A	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.982-5093T>C		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.982-5093T>C		intron	N/A	NP_001243082.1	P09917-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.982-5093T>C		intron	N/A	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.982-5093T>C		intron	N/A	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.1018-5093T>C		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114318 AN: 151436 Hom.: 43685 Cov.: 29

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.755 AC: 114437 AN: 151554 Hom.: 43743 Cov.: 29 AF XY: 0.753 AC XY: 55749 AN XY: 74006

African (AFR) AF: 0.865 AC: 35713 AN: 41284

American (AMR) AF: 0.777 AC: 11857 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2314 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3787 AN: 5166

South Asian (SAS) AF: 0.610 AC: 2920 AN: 4790

European-Finnish (FIN) AF: 0.763 AC: 7930 AN: 10388

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47514 AN: 67898

Other (OTH) AF: 0.740 AC: 1558 AN: 2106

Alfa AF: 0.726 Hom.: 22025

Bravo AF: 0.763

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.67
PhyloP100		-3.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4540799;

hg19: chr10-45930785;