chr13-30753685-C-T

Variant names:

• chr13-30753685-C-T
• rs9579649
• NM_001629.4:c.241+1563C>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.241+1563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,224 control chromosomes in the GnomAD database, including 498 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 0.075 (498 hom., cov: 33)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.241+1563C>T		intron_variant	Intron 3 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.412+1563C>T		intron_variant	Intron 4 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.121+1563C>T		intron_variant	Intron 3 of 4		XP_016876011.1
LOC124903146	XR_007063743.1	n.89+1826G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.241+1563C>T		intron_variant	Intron 3 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.412+1563C>T		intron_variant	Intron 4 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11342 AN: 152106 Hom.: 497 Cov.: 33

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0745 AC: 11345 AN: 152224 Hom.: 498 Cov.: 33 AF XY: 0.0711 AC XY: 5291 AN XY: 74436

African (AFR) AF: 0.0466 AC: 1937 AN: 41536

American (AMR) AF: 0.0473 AC: 724 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4830

European-Finnish (FIN) AF: 0.0987 AC: 1046 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7046 AN: 67994

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0750 Hom.: 207

Bravo AF: 0.0676

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.35
PhyloP100		-0.56
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: rs9579649; hg19: chr13-31327822; COSMIC: COSV66858337;