rs4769874

Variant names:

• chr13-30752304-G-A
• rs4769874
• NM_001629.4:c.241+182G>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.241+182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 152,276 control chromosomes in the GnomAD database, including 307 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 0.058 (307 hom., cov: 33)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 34 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]

LOC124903146 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.241+182G>A		intron_variant	Intron 3 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.412+182G>A		intron_variant	Intron 4 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.121+182G>A		intron_variant	Intron 3 of 4		XP_016876011.1
LOC124903146	XR_007063743.1	n.89+3207C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.241+182G>A		intron_variant	Intron 3 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.412+182G>A		intron_variant	Intron 4 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8759 AN: 152158 Hom.: 307 Cov.: 33

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0576 AC: 8771 AN: 152276 Hom.: 307 Cov.: 33 AF XY: 0.0572 AC XY: 4257 AN XY: 74476

African (AFR) AF: 0.0930 AC: 3866 AN: 41548

American (AMR) AF: 0.0466 AC: 713 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 242 AN: 3468

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5176

South Asian (SAS) AF: 0.109 AC: 524 AN: 4826

European-Finnish (FIN) AF: 0.0321 AC: 341 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2838 AN: 68018

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0518 Hom.: 111

Bravo AF: 0.0599

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.4
DANN	Benign	0.84
PhyloP100		-0.27
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: rs4769874; hg19: chr13-31326441;