rs743646

chr17-4632946-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001140.5(ALOX15):c.1455A>G(p.Thr485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,614,058 control chromosomes in the GnomAD database, including 9,366 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 0.078 (622 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8744 hom.)
• Consequence: ALOX15 NM_001140.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-4.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX15	NM_001140.5	c.1455A>G	p.Thr485=	synonymous_variant	11/14	ENST00000293761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000293761.8	c.1455A>G	p.Thr485=	synonymous_variant	11/14	1	NM_001140.5	P1
ALOX15	ENST00000570836.6	c.1455A>G	p.Thr485=	synonymous_variant	12/15	2		P1
ALOX15	ENST00000574640.1	c.1338A>G	p.Thr446=	synonymous_variant	11/14	2

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11949 AN: 152068 Hom.: 623 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0746

GnomAD3 exomes AF: 0.0846 AC: 21281 AN: 251444 Hom.: 1150 AF XY: 0.0875 AC XY: 11891 AN XY: 135892

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.0527

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0622

Gnomad FIN exome AF: 0.0955

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.0978

GnomAD4 exome AF: 0.105 AC: 153903 AN: 1461872 Hom.: 8744 Cov.: 33 AF XY: 0.105 AC XY: 76332 AN XY: 727240

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0555

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.0918

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0785 AC: 11945 AN: 152186 Hom.: 622 Cov.: 32 AF XY: 0.0776 AC XY: 5772 AN XY: 74394

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.109 Hom.: 1315

Bravo AF: 0.0741

Asia WGS AF: 0.0220 AC: 76 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.84
Dann	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs743646; hg19: chr17-4536241; COSMIC: COSV53399553; COSMIC: COSV53399553;