chr17-4639422-G-A

Position:

• chr17-4639422-G-A

Variant summary

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

The NM_001140.5(ALOX15):​c.337+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,605,980 control chromosomes in the GnomAD database, including 58,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (6769 hom., cov: 30)
  • Exomes 𝑓: 0.28 (51719 hom.)
• Consequence: ALOX15 NM_001140.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001208
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX15	NM_001140.5	c.337+8C>T		splice_region_variant, intron_variant		ENST00000293761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000293761.8	c.337+8C>T		splice_region_variant, intron_variant		1	NM_001140.5	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45108 AN: 151712 Hom.: 6768 Cov.: 30

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.300 AC: 74030 AN: 246988 Hom.: 10561 AF XY: 0.292 AC XY: 39197 AN XY: 134178

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.314

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.282 AC: 410191 AN: 1454152 Hom.: 51719 Cov.: 49 AF XY: 0.281 AC XY: 203443 AN XY: 723490

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.297 AC: 45133 AN: 151828 Hom.: 6769 Cov.: 30 AF XY: 0.298 AC XY: 22139 AN XY: 74174

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.285

Alfa AF: 0.287 Hom.: 9883

Bravo AF: 0.301

Asia WGS AF: 0.291 AC: 1011 AN: 3478

EpiCase AF: 0.277

EpiControl AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.73
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0040
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: rs11078528; hg19: chr17-4542717; COSMIC: COSV53396048; COSMIC: COSV53396048;