13-30756179-T-C

Position:

• chr13-30756179-T-C

Variant summary

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

The NM_001629.4(ALOX5AP):​c.323+154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,080 control chromosomes in the GnomAD database, including 38,334 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 0.71 (38334 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.323+154T>C		intron_variant		ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.494+154T>C		intron_variant			NP_001191335.1
ALOX5AP	XM_017020522.3	c.203+154T>C		intron_variant			XP_016876011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.323+154T>C		intron_variant		1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.494+154T>C		intron_variant		1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107254 AN: 151962 Hom.: 38313 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.706 AC: 107325 AN: 152080 Hom.: 38334 Cov.: 32 AF XY: 0.706 AC XY: 52525 AN XY: 74364

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.716

Alfa AF: 0.661 Hom.: 2531

Bravo AF: 0.700

Asia WGS AF: 0.729 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.63

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: rs4468448; hg19: chr13-31330316;