rs7919239

Positions:

• chr10-45402908-C-A
• chr10-45402908-C-T

Variant summary

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

The NM_000698.5(ALOX5):​c.431+6972C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,048 control chromosomes in the GnomAD database, including 4,072 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 0.23 (4072 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.431+6972C>A		intron_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.431+6972C>A		intron_variant		1	NM_000698.5	ENSP00000363512	P1
ALOX5	ENST00000542434.5	c.431+6972C>A		intron_variant		1		ENSP00000437634

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34526 AN: 151930 Hom.: 4063 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.227 AC: 34572 AN: 152048 Hom.: 4072 Cov.: 32 AF XY: 0.230 AC XY: 17120 AN XY: 74298

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.213

Alfa AF: 0.202 Hom.: 2169

Bravo AF: 0.218

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.76

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: rs7919239; hg19: chr10-45898356;