rs12430915

Positions:

• chr13-30726842-T-C

Variant summary

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

The ENST00000617770.4(ALOX5AP):​c.117-8709T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,142 control chromosomes in the GnomAD database, including 686 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 0.079 (686 hom., cov: 31)
• Consequence: ALOX5AP ENST00000617770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001204406.2	c.117-8709T>C		intron_variant			NP_001191335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.117-8709T>C		intron_variant		1		ENSP00000479870

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12051 AN: 152024 Hom.: 680 Cov.: 31

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0793 AC: 12066 AN: 152142 Hom.: 686 Cov.: 31 AF XY: 0.0815 AC XY: 6060 AN XY: 74368

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0742 Hom.: 62

Bravo AF: 0.0882

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12430915; hg19: chr13-31300979;