rs4356336

chr13-30745409-T-Cchr13-30745409-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ALOX5AP	NM_001629.4	c.170+1250T>C		intron_variant		ENST00000380490.5
LOC124903146	XR_007063743.1	n.90-770A>G		intron_variant, non_coding_transcript_variant
ALOX5AP	NM_001204406.2	c.341+1250T>C		intron_variant
ALOX5AP	XM_017020522.3	c.-70-1216T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.170+1250T>C		intron_variant		1	NM_001629.4	P1
ALOX5AP	ENST00000617770.4	c.341+1250T>C		intron_variant		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

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.503

Alfa AF: 0.466 Hom.: 2468

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4356336; hg19: chr13-31319546;