13-30735647-C-T

Variant names:

• chr13-30735647-C-T
• rs11542984
• NM_001629.4:c.42C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001629.4(ALOX5AP):​c.42C>T​(p.Ile14Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 1,614,124 control chromosomes in the GnomAD database, including 17 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 0.0045 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (9 hom.)
• Consequence: ALOX5AP NM_001629.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.82

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 13-30735647-C-T is Benign according to our data. Variant chr13-30735647-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041525.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000567 (829/1461886) while in subpopulation AFR AF = 0.0167 (560/33480). AF 95% confidence interval is 0.0156. There are 9 homozygotes in GnomAdExome4. There are 384 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.42C>T	p.Ile14Ile	synonymous_variant	Exon 1 of 5	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.213C>T	p.Ile71Ile	synonymous_variant	Exon 2 of 6		NP_001191335.1
LOC124903146	XR_007063743.1	n.221-2910G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.42C>T	p.Ile14Ile	synonymous_variant	Exon 1 of 5	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.213C>T	p.Ile71Ile	synonymous_variant	Exon 2 of 6	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 685 AN: 152120 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

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: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00122 AC: 306 AN: 251436 AF XY: 0.000920

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000567 AC: 829 AN: 1461886 Hom.: 9 Cov.: 35 AF XY: 0.000528 AC XY: 384 AN XY: 727240

African (AFR) AF: 0.0167 AC: 560 AN: 33480

American (AMR) AF: 0.000715 AC: 32 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00132 AC: 114 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1112006

Other (OTH) AF: 0.00149 AC: 90 AN: 60396

GnomAD4 genome AF: 0.00455 AC: 692 AN: 152238 Hom.: 8 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74436

African (AFR) AF: 0.0158 AC: 656 AN: 41540

American (AMR) AF: 0.00157 AC: 24 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00223 Hom.: 2

Bravo AF: 0.00515

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	-0.39
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		-4.8
PromoterAI		-0.22	Neutral
Mutation Taster		=100/0	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

Publications

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Other links and lift over

dbSNP: rs11542984; hg19: chr13-31309784; COSMIC: COSV66857946;