17-4636097-C-T

Position:

• chr17-4636097-C-T

Variant summary

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

The NM_001140.5(ALOX15):​c.952-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 960,116 control chromosomes in the GnomAD database, including 126,791 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 0.45 (16552 hom., cov: 31)
  • Exomes 𝑓: 0.52 (110239 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.952-129G>A		intron_variant		ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.952-129G>A		intron_variant		1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.952-129G>A		intron_variant		2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.835-129G>A		intron_variant		2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68618 AN: 151894 Hom.: 16551 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.517 AC: 417405 AN: 808104 Hom.: 110239 AF XY: 0.519 AC XY: 212351 AN XY: 409052

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.451 AC: 68630 AN: 152012 Hom.: 16552 Cov.: 31 AF XY: 0.455 AC XY: 33783 AN XY: 74310

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.456

Alfa AF: 0.427 Hom.: 2278

Bravo AF: 0.435

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.66

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: rs7217186; hg19: chr17-4539392; COSMIC: COSV53400369; COSMIC: COSV53400369;