rs2288619

Variant names:

• chr10-45444370-C-T
• rs2288619
• NM_000698.5:c.1845+84C>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.1845+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,448,798 control chromosomes in the GnomAD database, including 4,174 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 0.090 (827 hom., cov: 33)
  • Exomes 𝑓: 0.069 (3347 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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]

ENSG00000231964 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 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.1845+84C>T		intron	N/A	NP_000689.1
	ALOX5	NM_001320861.2		c.1758+84C>T		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.1749+84C>T		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.1845+84C>T		intron	N/A	ENSP00000363512.2
	ALOX5	ENST00000542434.5	TSL:1	c.1674+542C>T		intron	N/A	ENSP00000437634.1
	ALOX5	ENST00000851643.1		c.1881+84C>T		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13738 AN: 152182 Hom.: 821 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0223

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0686 AC: 88903 AN: 1296498 Hom.: 3347 Cov.: 26 AF XY: 0.0671 AC XY: 42242 AN XY: 629736

African (AFR) AF: 0.167 AC: 4770 AN: 28598

American (AMR) AF: 0.0440 AC: 1104 AN: 25090

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 765 AN: 19800

East Asian (EAS) AF: 0.0888 AC: 3034 AN: 34162

South Asian (SAS) AF: 0.0236 AC: 1564 AN: 66352

European-Finnish (FIN) AF: 0.0763 AC: 3043 AN: 39908

Middle Eastern (MID) AF: 0.0440 AC: 161 AN: 3662

European-Non Finnish (NFE) AF: 0.0692 AC: 70963 AN: 1025276

Other (OTH) AF: 0.0652 AC: 3499 AN: 53650

GnomAD4 genome AF: 0.0903 AC: 13759 AN: 152300 Hom.: 827 Cov.: 33 AF XY: 0.0893 AC XY: 6649 AN XY: 74468

African (AFR) AF: 0.162 AC: 6750 AN: 41548

American (AMR) AF: 0.0642 AC: 983 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.0520 AC: 269 AN: 5178

South Asian (SAS) AF: 0.0221 AC: 107 AN: 4832

European-Finnish (FIN) AF: 0.0689 AC: 732 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0667 AC: 4540 AN: 68024

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0783 Hom.: 697

Bravo AF: 0.0940

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-1.5
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: rs2288619; hg19: chr10-45939818;