rs4769058

chr13-30759294-T-C

Variant summary

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

The NM_001629.4(ALOX5AP):c.323+3269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,234 control chromosomes in the GnomAD database, including 730 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 0.078 (730 hom., cov: 31)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5AP	NM_001629.4	c.323+3269T>C		intron_variant		ENST00000380490.5
ALOX5AP	NM_001204406.2	c.494+3269T>C		intron_variant
ALOX5AP	XM_017020522.3	c.203+3269T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.323+3269T>C		intron_variant		1	NM_001629.4	P1
ALOX5AP	ENST00000617770.4	c.494+3269T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11908 AN: 152116 Hom.: 725 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0784 AC: 11933 AN: 152234 Hom.: 730 Cov.: 31 AF XY: 0.0773 AC XY: 5750 AN XY: 74420

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0419

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0684 Hom.: 131

Bravo AF: 0.0830

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.8
Dann	Benign	0.74

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: rs4769058; hg19: chr13-31333431;