rs9551963

Positions:

• chr13-30758410-A-C
• chr13-30758410-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.323+2385A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,056 control chromosomes in the GnomAD database, including 19,172 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 (19172 hom., cov: 31)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.323+2385A>C		intron_variant		ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.494+2385A>C		intron_variant			NP_001191335.1
ALOX5AP	XM_017020522.3	c.203+2385A>C		intron_variant			XP_016876011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.323+2385A>C		intron_variant		1	NM_001629.4	ENSP00000369858	P1
ALOX5AP	ENST00000617770.4	c.494+2385A>C		intron_variant		1		ENSP00000479870

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76064 AN: 151938 Hom.: 19151 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.501 AC: 76133 AN: 152056 Hom.: 19172 Cov.: 31 AF XY: 0.497 AC XY: 36944 AN XY: 74338

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.491

Alfa AF: 0.500 Hom.: 16739

Bravo AF: 0.504

Asia WGS AF: 0.378 AC: 1313 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	0.17
DANN	Benign	0.31

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: rs9551963; hg19: chr13-31332547;