chr13-30740037-G-A

Variant names:

• chr13-30740037-G-A
• rs4503649
• NM_001629.4:c.71-4023G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.71-4023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,104 control chromosomes in the GnomAD database, including 4,061 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 0.22 (4061 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 10 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]

LOC124903146 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.71-4023G>A		intron_variant	Intron 1 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.242-4023G>A		intron_variant	Intron 2 of 5		NP_001191335.1
LOC124903146	XR_007063743.1	n.220+4472C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.71-4023G>A		intron_variant	Intron 1 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.242-4023G>A		intron_variant	Intron 2 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33629 AN: 151986 Hom.: 4052 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.221 AC: 33664 AN: 152104 Hom.: 4061 Cov.: 32 AF XY: 0.227 AC XY: 16854 AN XY: 74372

African (AFR) AF: 0.128 AC: 5301 AN: 41498

American (AMR) AF: 0.258 AC: 3934 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.364 AC: 1876 AN: 5158

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2741 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16542 AN: 67972

Other (OTH) AF: 0.248 AC: 524 AN: 2116

Alfa AF: 0.235 Hom.: 7392

Bravo AF: 0.217

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.71
PhyloP100		0.26
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: rs4503649; hg19: chr13-31314174;