13-30738041-A-T

Variant names:

• chr13-30738041-A-T
• rs12429692
• NM_001629.4:c.70+2366A>T

Variant summary

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

The NM_001629.4(ALOX5AP):​c.70+2366A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,990 control chromosomes in the GnomAD database, including 4,763 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 0.25 (4763 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 27 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.70+2366A>T		intron_variant	Intron 1 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.241+2366A>T		intron_variant	Intron 2 of 5		NP_001191335.1
LOC124903146	XR_007063743.1	n.221-5304T>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.70+2366A>T		intron_variant	Intron 1 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.241+2366A>T		intron_variant	Intron 2 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37415 AN: 151872 Hom.: 4757 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.246 AC: 37426 AN: 151990 Hom.: 4763 Cov.: 32 AF XY: 0.251 AC XY: 18622 AN XY: 74292

African (AFR) AF: 0.198 AC: 8192 AN: 41444

American (AMR) AF: 0.294 AC: 4486 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1790 AN: 5166

South Asian (SAS) AF: 0.285 AC: 1370 AN: 4812

European-Finnish (FIN) AF: 0.255 AC: 2688 AN: 10546

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17108 AN: 67962

Other (OTH) AF: 0.242 AC: 510 AN: 2106

Alfa AF: 0.234 Hom.: 598

Bravo AF: 0.249

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-1.3
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: rs12429692; hg19: chr13-31312178;