rs4254165

Variant names:

• chr13-30743741-A-G
• rs4254165
• NM_001629.4:c.71-319A>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.71-319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,802 control chromosomes in the GnomAD database, including 7,067 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 0.30 (7067 hom., cov: 30)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001629.4. 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_001629.4	MANE Select	c.71-319A>G		intron	N/A	NP_001620.2
	ALOX5AP	NM_001204406.2		c.242-319A>G		intron	N/A	NP_001191335.1	A0A087WW23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	ENST00000380490.5	TSL:1 MANE Select	c.71-319A>G		intron	N/A	ENSP00000369858.3	P20292
	ALOX5AP	ENST00000617770.4	TSL:1	c.242-319A>G		intron	N/A	ENSP00000479870.1	A0A087WW23
	ALOX5AP	ENST00000892335.1		c.71-319A>G		intron	N/A	ENSP00000562394.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45502 AN: 151684 Hom.: 7049 Cov.: 30

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.300 AC: 45558 AN: 151802 Hom.: 7067 Cov.: 30 AF XY: 0.301 AC XY: 22320 AN XY: 74132

African (AFR) AF: 0.220 AC: 9101 AN: 41390

American (AMR) AF: 0.306 AC: 4665 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2106 AN: 5122

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3429 AN: 10492

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22565 AN: 67948

Other (OTH) AF: 0.330 AC: 695 AN: 2106

Alfa AF: 0.317 Hom.: 10106

Bravo AF: 0.294

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.010
DANN	Benign	0.70
PhyloP100		-3.6
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: rs4254165; hg19: chr13-31317878; COSMIC: COSV66858324;