rs4769873

Positions:

• chr13-30738552-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.70+2877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,208 control chromosomes in the GnomAD database, including 1,493 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 0.11 (1493 hom., cov: 32)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.70+2877C>T		intron_variant		ENST00000380490.5	NP_001620.2
LOC124903146	XR_007063743.1	n.221-5815G>A		intron_variant, non_coding_transcript_variant
ALOX5AP	NM_001204406.2	c.241+2877C>T		intron_variant			NP_001191335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.70+2877C>T		intron_variant		1	NM_001629.4	ENSP00000369858	P1
ALOX5AP	ENST00000617770.4	c.241+2877C>T		intron_variant		1		ENSP00000479870

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16700 AN: 152090 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.110 AC: 16741 AN: 152208 Hom.: 1493 Cov.: 32 AF XY: 0.107 AC XY: 7996 AN XY: 74422

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0805

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0727 Hom.: 776

Bravo AF: 0.121

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.48

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: rs4769873; hg19: chr13-31312689;