rs2664593

chr17-4641837-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000574640.1(ALOX15):c.-186G>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 0.204 in 726,100 control chromosomes in the GnomAD database, including 16,093 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 0.19 (2953 hom., cov: 31)
  • Exomes 𝑓: 0.21 (13140 hom.)
• Consequence: ALOX15 ENST00000574640.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

Genes affected

ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000574640.1	c.-186G>C		5_prime_UTR_variant	1/14	2
ALOX15	ENST00000570836.6	c.-25-161G>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29028 AN: 151818 Hom.: 2947 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.207 AC: 118959 AN: 574164 Hom.: 13140 Cov.: 7 AF XY: 0.211 AC XY: 62423 AN XY: 296252

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.191 AC: 29055 AN: 151936 Hom.: 2953 Cov.: 31 AF XY: 0.193 AC XY: 14355 AN XY: 74258

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.188

Alfa AF: 0.197 Hom.: 423

Bravo AF: 0.187

Asia WGS AF: 0.232 AC: 806 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	6.3
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2664593; hg19: chr17-4545132;