chr13-30760561-C-A

Variant names:

• chr13-30760561-C-A
• rs9508835
• NM_001629.4:c.324-3383C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.324-3383C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,194 control chromosomes in the GnomAD database, including 5,386 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 0.24 (5386 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.324-3383C>A		intron_variant	Intron 4 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.495-3383C>A		intron_variant	Intron 5 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.204-3383C>A		intron_variant	Intron 4 of 4		XP_016876011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.324-3383C>A		intron_variant	Intron 4 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.495-3383C>A		intron_variant	Intron 5 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36060 AN: 152078 Hom.: 5384 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.237 AC: 36069 AN: 152194 Hom.: 5386 Cov.: 32 AF XY: 0.239 AC XY: 17781 AN XY: 74400

African (AFR) AF: 0.0563 AC: 2338 AN: 41548

American (AMR) AF: 0.322 AC: 4934 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1293 AN: 5172

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4822

European-Finnish (FIN) AF: 0.323 AC: 3419 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21187 AN: 67980

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.286 Hom.: 19387

Bravo AF: 0.231

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9508835; hg19: chr13-31334698;