rs4076128

Positions:

• chr13-30731006-A-G

Variant summary

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

The ENST00000617770.4(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 ENST00000617770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5AP	NM_001204406.2	c.117-4545A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.117-4545A>G		intron_variant		1

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

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.380

Alfa AF: 0.318 Hom.: 1910

Bravo AF: 0.437

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4076128; hg19: chr13-31305143;