rs4076128

Variant names:

• chr13-30731006-A-G
• rs4076128
• ENST00000617770.4:c.117-4545A>G

Variant summary

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

The NM_001204406.2(ALOX5AP):​c.117-4545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 150,424 control chromosomes in the GnomAD database, including 16,607 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 0.42 (16607 hom., cov: 32)
• Consequence: ALOX5AP NM_001204406.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204406.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	NM_001204406.2		c.117-4545A>G		intron	N/A	NP_001191335.1	A0A087WW23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	ENST00000617770.4	TSL:1	c.117-4545A>G		intron	N/A	ENSP00000479870.1	A0A087WW23

Frequencies

GnomAD3 genomes AF: 0.418 AC: 62790 AN: 150298 Hom.: 16580 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.418 AC: 62869 AN: 150424 Hom.: 16607 Cov.: 32 AF XY: 0.417 AC XY: 30603 AN XY: 73450

African (AFR) AF: 0.757 AC: 31299 AN: 41356

American (AMR) AF: 0.340 AC: 5153 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1202 AN: 3446

East Asian (EAS) AF: 0.372 AC: 1869 AN: 5026

South Asian (SAS) AF: 0.493 AC: 2344 AN: 4752

European-Finnish (FIN) AF: 0.225 AC: 2257 AN: 10034

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17628 AN: 67376

Other (OTH) AF: 0.380 AC: 796 AN: 2096

Alfa AF: 0.316 Hom.: 3167

Bravo AF: 0.437

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.9
DANN	Benign	0.52
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4076128; hg19: chr13-31305143;