rs4356336

Variant names:

• chr13-30745409-T-C
• rs4356336
• NM_001629.4:c.170+1250T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-30745409-T-C
• chr13-30745409-T-G

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+1250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,456 control chromosomes in the GnomAD database, including 18,833 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 0.49 (18833 hom., cov: 31)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 2 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 = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.170+1250T>C		intron_variant	Intron 2 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.341+1250T>C		intron_variant	Intron 3 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.-70-1216T>C		intron_variant	Intron 1 of 4		XP_016876011.1
LOC124903146	XR_007063743.1	n.90-770A>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+1250T>C		intron_variant	Intron 2 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.341+1250T>C		intron_variant	Intron 3 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74821 AN: 151334 Hom.: 18819 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.494 AC: 74893 AN: 151456 Hom.: 18833 Cov.: 31 AF XY: 0.499 AC XY: 36941 AN XY: 74004

African (AFR) AF: 0.571 AC: 23550 AN: 41264

American (AMR) AF: 0.495 AC: 7538 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1684 AN: 3456

East Asian (EAS) AF: 0.622 AC: 3184 AN: 5118

South Asian (SAS) AF: 0.578 AC: 2780 AN: 4810

European-Finnish (FIN) AF: 0.437 AC: 4577 AN: 10468

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

European-Non Finnish (NFE) AF: 0.443 AC: 30054 AN: 67820

Other (OTH) AF: 0.503 AC: 1059 AN: 2104

Alfa AF: 0.468 Hom.: 2577

Bravo AF: 0.504

Asia WGS AF: 0.623 AC: 2171 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	4.5
DANN	Benign	0.36
PhyloP100		0.071
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: rs4356336; hg19: chr13-31319546;