13-30735566-T-C

Variant names:

• chr13-30735566-T-C
• rs78236471
• ENST00000617770.4:c.132T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001629.4(ALOX5AP):​c.-40T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000824 in 1,613,206 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (8 hom.)
• Consequence: ALOX5AP NM_001629.4 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.100
• 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]

LOC124903146 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-30735566-T-C is Benign according to our data. Variant chr13-30735566-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041867.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.-40T>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.132T>C	p.Ala44Ala	synonymous_variant	Exon 2 of 6		NP_001191335.1
LOC124903146	XR_007063743.1	n.221-2829A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000617770.4	c.132T>C	p.Ala44Ala	synonymous_variant	Exon 2 of 6	1		ENSP00000479870.1
ALOX5AP	ENST00000380490.5	c.-40T>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_001629.4	ENSP00000369858.3

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 599 AN: 152030 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00107 AC: 268 AN: 249872 AF XY: 0.000800

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000495 AC: 723 AN: 1461060 Hom.: 8 Cov.: 35 AF XY: 0.000465 AC XY: 338 AN XY: 726690

African (AFR) AF: 0.0142 AC: 474 AN: 33470

American (AMR) AF: 0.000717 AC: 32 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00131 AC: 113 AN: 85968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111684

Other (OTH) AF: 0.00134 AC: 81 AN: 60384

GnomAD4 genome AF: 0.00398 AC: 606 AN: 152146 Hom.: 7 Cov.: 32 AF XY: 0.00394 AC XY: 293 AN XY: 74374

African (AFR) AF: 0.0139 AC: 575 AN: 41512

American (AMR) AF: 0.00144 AC: 22 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00141 Hom.: 3

Bravo AF: 0.00440

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ALOX5AP-related disorder Benign:1

Dec 04, 2023

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	-0.82
CADD	Benign	5.8
DANN	Benign	0.61
PhyloP100		-0.10
PromoterAI		0.23	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs78236471; hg19: chr13-31309703;