13-30737636-C-G

Variant names:

• chr13-30737636-C-G
• rs4293222
• NM_001629.4:c.70+1961C>G

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+1961C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,934 control chromosomes in the GnomAD database, including 24,628 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 0.54 (24628 hom., cov: 31)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.70+1961C>G		intron_variant	Intron 1 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.241+1961C>G		intron_variant	Intron 2 of 5		NP_001191335.1
LOC124903146	XR_007063743.1	n.221-4899G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.70+1961C>G		intron_variant	Intron 1 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.241+1961C>G		intron_variant	Intron 2 of 5	1		ENSP00000479870.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81973 AN: 151816 Hom.: 24623 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.540 AC: 82014 AN: 151934 Hom.: 24628 Cov.: 31 AF XY: 0.541 AC XY: 40181 AN XY: 74246

African (AFR) AF: 0.259 AC: 10718 AN: 41410

American (AMR) AF: 0.525 AC: 8027 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3153 AN: 5144

South Asian (SAS) AF: 0.595 AC: 2870 AN: 4820

European-Finnish (FIN) AF: 0.704 AC: 7425 AN: 10548

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45905 AN: 67956

Other (OTH) AF: 0.557 AC: 1169 AN: 2100

Alfa AF: 0.492 Hom.: 1655

Bravo AF: 0.509

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.44
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: rs4293222; hg19: chr13-31311773; COSMIC: COSV66858323; COSMIC: COSV66858323;