chr13-30713842-G-GTA

Variant names:

• chr13-30713842-G-GTA
• rs60649469
• ENST00000617770.4:c.116+1_116+2insTA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The ENST00000617770.4(ALOX5AP):​c.116+1_116+2insTA variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,447,104 control chromosomes in the GnomAD database, including 383,826 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (33952 hom., cov: 0)
  • Exomes 𝑓: 0.73 (349874 hom.)
• Consequence: ALOX5AP ENST00000617770.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.55403346 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.1, offset of 0 (no position change), new splice context is: ctgGTatgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001204406.2	c.116+2_116+3insAT		splice_region_variant, intron_variant	Intron 1 of 5		NP_001191335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.116+1_116+2insTA		splice_donor_variant, intron_variant	Intron 1 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 97551 AN: 132946 Hom.: 33937 Cov.: 0

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.738

GnomAD2 exomes AF: 0.721 AC: 80594 AN: 111854 AF XY: 0.718

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.727

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.676

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.769

Gnomad OTH exome AF: 0.725

GnomAD4 exome AF: 0.733 AC: 962611 AN: 1314060 Hom.: 349874 Cov.: 49 AF XY: 0.730 AC XY: 473016 AN XY: 648312

African (AFR) AF: 0.350 AC: 10552 AN: 30120

American (AMR) AF: 0.671 AC: 22845 AN: 34024

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 16416 AN: 23876

East Asian (EAS) AF: 0.641 AC: 21759 AN: 33930

South Asian (SAS) AF: 0.580 AC: 43856 AN: 75668

European-Finnish (FIN) AF: 0.801 AC: 25235 AN: 31510

Middle Eastern (MID) AF: 0.624 AC: 3437 AN: 5510

European-Non Finnish (NFE) AF: 0.762 AC: 780160 AN: 1024386

Other (OTH) AF: 0.697 AC: 38351 AN: 55036

GnomAD4 genome AF: 0.734 AC: 97613 AN: 133044 Hom.: 33952 Cov.: 0 AF XY: 0.734 AC XY: 47865 AN XY: 65222

African (AFR) AF: 0.531 AC: 14712 AN: 27684

American (AMR) AF: 0.764 AC: 10774 AN: 14094

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2400 AN: 3196

East Asian (EAS) AF: 0.711 AC: 3325 AN: 4676

South Asian (SAS) AF: 0.671 AC: 2792 AN: 4164

European-Finnish (FIN) AF: 0.831 AC: 8671 AN: 10436

Middle Eastern (MID) AF: 0.738 AC: 186 AN: 252

European-Non Finnish (NFE) AF: 0.800 AC: 52609 AN: 65726

Other (OTH) AF: 0.739 AC: 1424 AN: 1928

Alfa AF: 0.585 Hom.: 1554

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60649469; hg19: chr13-31287979;