NM_000698.5:c.150+2333T>A

Variant names:

• chr10-45376762-T-A
• rs12783095
• NM_000698.5:c.150+2333T>A

Variant summary

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

The NM_000698.5(ALOX5):​c.150+2333T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,026 control chromosomes in the GnomAD database, including 2,200 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 0.17 (2200 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 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.150+2333T>A		intron	N/A	NP_000689.1
	ALOX5	NM_001320861.2		c.150+2333T>A		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.150+2333T>A		intron	N/A	NP_001243082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.150+2333T>A		intron	N/A	ENSP00000363512.2
	ALOX5	ENST00000542434.5	TSL:1	c.150+2333T>A		intron	N/A	ENSP00000437634.1
	ALOX5	ENST00000851643.1		c.150+2333T>A		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25389 AN: 151908 Hom.: 2195 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.167 AC: 25418 AN: 152026 Hom.: 2200 Cov.: 32 AF XY: 0.169 AC XY: 12525 AN XY: 74298

African (AFR) AF: 0.175 AC: 7251 AN: 41474

American (AMR) AF: 0.133 AC: 2040 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.183 AC: 943 AN: 5164

South Asian (SAS) AF: 0.189 AC: 907 AN: 4804

European-Finnish (FIN) AF: 0.194 AC: 2044 AN: 10548

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11066 AN: 67970

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.161 Hom.: 256

Bravo AF: 0.162

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.48
PhyloP100		-0.23
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: rs12783095; hg19: chr10-45872210;