13-30756179-T-C

Variant names:

• chr13-30756179-T-C
• rs4468448
• NM_001629.4:c.323+154T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.323+154T>C		intron	N/A	NP_001620.2
	ALOX5AP	NM_001204406.2		c.494+154T>C		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.323+154T>C		intron	N/A	ENSP00000369858.3	P20292
	ALOX5AP	ENST00000617770.4	TSL:1	c.494+154T>C		intron	N/A	ENSP00000479870.1	A0A087WW23
	ALOX5AP	ENST00000892335.1		c.323+154T>C		intron	N/A	ENSP00000562394.1

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

African (AFR) AF: 0.582 AC: 24138 AN: 41444

American (AMR) AF: 0.736 AC: 11253 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4058 AN: 5174

South Asian (SAS) AF: 0.690 AC: 3328 AN: 4820

European-Finnish (FIN) AF: 0.771 AC: 8169 AN: 10594

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51376 AN: 67978

Other (OTH) AF: 0.716 AC: 1514 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.63
PhyloP100		-0.46
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: rs4468448; hg19: chr13-31330316;