rs2619118

Positions:

• chr17-4636982-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.951+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,088,368 control chromosomes in the GnomAD database, including 141,648 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 0.44 (15723 hom., cov: 32)
  • Exomes 𝑓: 0.51 (125925 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.951+133G>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.951+133G>A		intron_variant		1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.951+133G>A		intron_variant		2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.834+133G>A		intron_variant		2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66470 AN: 151888 Hom.: 15721 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.515 AC: 481940 AN: 936360 Hom.: 125925 AF XY: 0.518 AC XY: 244162 AN XY: 471640

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.437 AC: 66487 AN: 152008 Hom.: 15723 Cov.: 32 AF XY: 0.441 AC XY: 32737 AN XY: 74280

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.441

Alfa AF: 0.470 Hom.: 2407

Bravo AF: 0.417

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.74

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: rs2619118; hg19: chr17-4540277; COSMIC: COSV53398938; COSMIC: COSV53398938;