chr13-30713844-G-A

Variant names:

• chr13-30713844-G-A
• rs73163047
• ENST00000617770.4:c.116+3G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001204406.2(ALOX5AP):​c.116+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 650,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: ALOX5AP NM_001204406.2 splice_region, intron
• Scores: Splicing: ADA: 0.00008935
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.74
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-30713844-G-A is Benign according to our data. Variant chr13-30713844-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041316.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001204406.2	c.116+3G>A		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+3G>A		splice_region_variant, intron_variant	Intron 1 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 9 AN: 75632 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000545 AC: 59 AN: 108216 AF XY: 0.000553

Gnomad AFR exome AF: 0.000381

Gnomad AMR exome AF: 0.000932

Gnomad ASJ exome AF: 0.000144

Gnomad EAS exome AF: 0.000228

Gnomad FIN exome AF: 0.000211

Gnomad NFE exome AF: 0.000664

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00109 AC: 629 AN: 575048 Hom.: 0 Cov.: 33 AF XY: 0.00102 AC XY: 294 AN XY: 287098

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000235 AC: 6 AN: 25502

American (AMR) AF: 0.00240 AC: 50 AN: 20792

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 25 AN: 12426

East Asian (EAS) AF: 0.00168 AC: 31 AN: 18434

South Asian (SAS) AF: 0.000503 AC: 23 AN: 45750

European-Finnish (FIN) AF: 0.000309 AC: 4 AN: 12950

Middle Eastern (MID) AF: 0.000933 AC: 3 AN: 3214

European-Non Finnish (NFE) AF: 0.00110 AC: 450 AN: 408498

Other (OTH) AF: 0.00135 AC: 37 AN: 27482

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000119 AC: 9 AN: 75632 Hom.: 0 Cov.: 24 AF XY: 0.000136 AC XY: 5 AN XY: 36740

African (AFR) AF: 0.000167 AC: 5 AN: 30030

American (AMR) AF: 0.00 AC: 0 AN: 6716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1696

East Asian (EAS) AF: 0.00 AC: 0 AN: 2498

South Asian (SAS) AF: 0.00 AC: 0 AN: 2634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.000147 AC: 4 AN: 27176

Other (OTH) AF: 0.00 AC: 0 AN: 966

Alfa AF: 0.296 Hom.: 3423

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ALOX5AP-related disorder Benign:1

Jul 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		1.7
PromoterAI		0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000089
dbscSNV1_RF	Benign	0.062

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

Other links and lift over

dbSNP: rs73163047; hg19: chr13-31287981; COSMIC: COSV62486131;