13-30735693-C-A

Variant names:

• chr13-30735693-C-A
• rs4769055
• NM_001629.4:c.70+18C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.70+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,612,760 control chromosomes in the GnomAD database, including 112,249 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 0.46 (19246 hom., cov: 32)
  • Exomes 𝑓: 0.34 (93003 hom.)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.70+18C>A		intron_variant	Intron 1 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.241+18C>A		intron_variant	Intron 2 of 5		NP_001191335.1
LOC124903146	XR_007063743.1	n.221-2956G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.70+18C>A		intron_variant	Intron 1 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.241+18C>A		intron_variant	Intron 2 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70400 AN: 151914 Hom.: 19218 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.436

GnomAD2 exomes AF: 0.414 AC: 103658 AN: 250426 AF XY: 0.404

Gnomad AFR exome AF: 0.768

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.532

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.342 AC: 500231 AN: 1460728 Hom.: 93003 Cov.: 37 AF XY: 0.344 AC XY: 250128 AN XY: 726650

African (AFR) AF: 0.772 AC: 25813 AN: 33458

American (AMR) AF: 0.555 AC: 24768 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9659 AN: 26098

East Asian (EAS) AF: 0.519 AC: 20598 AN: 39692

South Asian (SAS) AF: 0.474 AC: 40856 AN: 86206

European-Finnish (FIN) AF: 0.295 AC: 15736 AN: 53392

Middle Eastern (MID) AF: 0.438 AC: 2529 AN: 5768

European-Non Finnish (NFE) AF: 0.304 AC: 337583 AN: 1111164

Other (OTH) AF: 0.376 AC: 22689 AN: 60336

GnomAD4 genome AF: 0.464 AC: 70487 AN: 152032 Hom.: 19246 Cov.: 32 AF XY: 0.465 AC XY: 34579 AN XY: 74314

African (AFR) AF: 0.761 AC: 31557 AN: 41480

American (AMR) AF: 0.475 AC: 7251 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2614 AN: 5152

South Asian (SAS) AF: 0.494 AC: 2377 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3121 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20765 AN: 67976

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.356 Hom.: 45079

Bravo AF: 0.494

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.34
PhyloP100		0.22
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4769055; hg19: chr13-31309830;