rs4254165

Positions:

• chr13-30743741-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.71-319A>G		intron_variant		ENST00000380490.5	NP_001620.2
LOC124903146	XR_007063743.1	n.220+768T>C		intron_variant, non_coding_transcript_variant
ALOX5AP	NM_001204406.2	c.242-319A>G		intron_variant			NP_001191335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.71-319A>G		intron_variant		1	NM_001629.4	ENSP00000369858	P1
ALOX5AP	ENST00000617770.4	c.242-319A>G		intron_variant		1		ENSP00000479870
ALOX5AP	ENST00000479597.1	n.211-319A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.330

Alfa AF: 0.319 Hom.: 7914

Bravo AF: 0.294

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.010
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4254165; hg19: chr13-31317878; COSMIC: COSV66858324;