chr13-30729374-C-T

Position:

• chr13-30729374-C-T

Variant summary

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

The ENST00000617770.4(ALOX5AP):​c.117-6177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,008 control chromosomes in the GnomAD database, including 4,230 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 0.21 (4230 hom., cov: 32)
• Consequence: ALOX5AP ENST00000617770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

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 (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5AP	NM_001204406.2	c.117-6177C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.117-6177C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31205 AN: 151892 Hom.: 4211 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.206 AC: 31261 AN: 152008 Hom.: 4230 Cov.: 32 AF XY: 0.205 AC XY: 15210 AN XY: 74306

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.201

Alfa AF: 0.180 Hom.: 668

Bravo AF: 0.224

Asia WGS AF: 0.286 AC: 992 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	0.21
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4769870; hg19: chr13-31303511;