rs4769055

Positions:

• chr13-30735693-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.70+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,612,760 control chromosomes in the GnomAD database, including 112,249 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 0.46 (19246 hom., cov: 32)
  • Exomes 𝑓: 0.34 (93003 hom.)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.70+18C>A		intron_variant		ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.241+18C>A		intron_variant			NP_001191335.1
LOC124903146	XR_007063743.1	n.221-2956G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.70+18C>A		intron_variant		1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.241+18C>A		intron_variant		1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70400 AN: 151914 Hom.: 19218 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.436

GnomAD3 exomes AF: 0.414 AC: 103658 AN: 250426 Hom.: 23957 AF XY: 0.404 AC XY: 54693 AN XY: 135308

Gnomad AFR exome AF: 0.768

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.532

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.342 AC: 500231 AN: 1460728 Hom.: 93003 Cov.: 37 AF XY: 0.344 AC XY: 250128 AN XY: 726650

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.464 AC: 70487 AN: 152032 Hom.: 19246 Cov.: 32 AF XY: 0.465 AC XY: 34579 AN XY: 74314

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.434

Alfa AF: 0.341 Hom.: 19892

Bravo AF: 0.494

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.34

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: rs4769055; hg19: chr13-31309830;