13-30761908-A-G

Variant names:

• chr13-30761908-A-G
• rs9315050
• NM_001629.4:c.324-2036A>G

Variant summary

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

The NM_001629.4(ALOX5AP):​c.324-2036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,260 control chromosomes in the GnomAD database, including 1,306 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 0.11 (1306 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 16 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.324-2036A>G		intron_variant	Intron 4 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.495-2036A>G		intron_variant	Intron 5 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.204-2036A>G		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.324-2036A>G		intron_variant	Intron 4 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.495-2036A>G		intron_variant	Intron 5 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16818 AN: 152142 Hom.: 1301 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.111 AC: 16845 AN: 152260 Hom.: 1306 Cov.: 32 AF XY: 0.109 AC XY: 8128 AN XY: 74458

African (AFR) AF: 0.217 AC: 9033 AN: 41534

American (AMR) AF: 0.0793 AC: 1213 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5188

South Asian (SAS) AF: 0.115 AC: 555 AN: 4820

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4484 AN: 68022

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0842 Hom.: 687

Bravo AF: 0.117

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.14
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: rs9315050; hg19: chr13-31336045;