17-4632090-A-G

Position:

• chr17-4632090-A-G

Variant summary

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

The NM_001140.5(ALOX15):​c.1642-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,608,558 control chromosomes in the GnomAD database, including 229,305 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 (22061 hom., cov: 33)
  • Exomes 𝑓: 0.53 (207244 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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 (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1642-34T>C		intron_variant		ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1642-34T>C		intron_variant		1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1642-34T>C		intron_variant		2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1525-34T>C		intron_variant		2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81791 AN: 151990 Hom.: 22051 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.522

GnomAD3 exomes AF: 0.530 AC: 131182 AN: 247592 Hom.: 34938 AF XY: 0.531 AC XY: 71021 AN XY: 133696

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.582

Gnomad SAS exome AF: 0.536

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.533

GnomAD4 exome AF: 0.533 AC: 775964 AN: 1456450 Hom.: 207244 Cov.: 50 AF XY: 0.532 AC XY: 385259 AN XY: 723680

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.538 AC: 81832 AN: 152108 Hom.: 22061 Cov.: 33 AF XY: 0.539 AC XY: 40051 AN XY: 74362

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.523

Alfa AF: 0.530 Hom.: 22740

Bravo AF: 0.540

Asia WGS AF: 0.541 AC: 1883 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	1.5
DANN	Benign	0.38

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: rs2619112; hg19: chr17-4535385; COSMIC: COSV53400348;