13-30745981-T-C

Variant names:

• chr13-30745981-T-C
• rs4147064
• NM_001629.4:c.170+1822T>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.170+1822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,076 control chromosomes in the GnomAD database, including 19,182 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 0.50 (19182 hom., cov: 33)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.170+1822T>C		intron_variant	Intron 2 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.341+1822T>C		intron_variant	Intron 3 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.-70-644T>C		intron_variant	Intron 1 of 4		XP_016876011.1
LOC124903146	XR_007063743.1	n.90-1342A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.170+1822T>C		intron_variant	Intron 2 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.341+1822T>C		intron_variant	Intron 3 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75520 AN: 151958 Hom.: 19168 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.497 AC: 75591 AN: 152076 Hom.: 19182 Cov.: 33 AF XY: 0.502 AC XY: 37307 AN XY: 74332

African (AFR) AF: 0.576 AC: 23893 AN: 41486

American (AMR) AF: 0.498 AC: 7604 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3232 AN: 5178

South Asian (SAS) AF: 0.577 AC: 2789 AN: 4832

European-Finnish (FIN) AF: 0.441 AC: 4645 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30199 AN: 67974

Other (OTH) AF: 0.503 AC: 1065 AN: 2116

Alfa AF: 0.471 Hom.: 3340

Bravo AF: 0.505

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.59
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: rs4147064; hg19: chr13-31320118;