rs4073259

Positions:

• chr13-30732134-G-A

Variant summary

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

The NM_001204406.2(ALOX5AP):​c.117-3417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,190 control chromosomes in the GnomAD database, including 21,664 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 0.50 (21664 hom., cov: 33)
• Consequence: ALOX5AP NM_001204406.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

Genes affected

ALOX5AP (HGNC:436): (arachidonate 5-lipoxygenase activating protein) This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001204406.2	c.117-3417G>A		intron_variant			NP_001191335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.117-3417G>A		intron_variant		1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75655 AN: 152072 Hom.: 21663 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.497 AC: 75678 AN: 152190 Hom.: 21664 Cov.: 33 AF XY: 0.497 AC XY: 37002 AN XY: 74408

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.528

Alfa AF: 0.574 Hom.: 3394

Bravo AF: 0.466

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4073259; hg19: chr13-31306271;