rs11239523

Positions:

• chr10-45416789-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):​c.554+4476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,728 control chromosomes in the GnomAD database, including 1,593 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 0.14 (1593 hom., cov: 31)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.554+4476T>C		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.554+4476T>C		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.554+4476T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20608 AN: 151610 Hom.: 1590 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.136 AC: 20627 AN: 151728 Hom.: 1593 Cov.: 31 AF XY: 0.139 AC XY: 10276 AN XY: 74160

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.123

Alfa AF: 0.143 Hom.: 365

Bravo AF: 0.122

Asia WGS AF: 0.0410 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs11239523; hg19: chr10-45912237;