rs4769060

Positions:

• chr13-30763740-A-G
• chr13-30763740-A-T

Variant summary

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

The NM_001629.4(ALOX5AP):​c.324-204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,980 control chromosomes in the GnomAD database, including 10,960 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 0.35 (10960 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5AP	NM_001629.4	c.324-204A>G		intron_variant		ENST00000380490.5
ALOX5AP	NM_001204406.2	c.495-204A>G		intron_variant
ALOX5AP	XM_017020522.3	c.204-204A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.324-204A>G		intron_variant		1	NM_001629.4	P1
ALOX5AP	ENST00000617770.4	c.495-204A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53500 AN: 151862 Hom.: 10954 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.352 AC: 53521 AN: 151980 Hom.: 10960 Cov.: 32 AF XY: 0.352 AC XY: 26170 AN XY: 74276

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.351

Alfa AF: 0.416 Hom.: 14852

Bravo AF: 0.344

Asia WGS AF: 0.288 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.59

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: rs4769060; hg19: chr13-31337877;