rs11078527

chr17-4637352-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.808-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,389,162 control chromosomes in the GnomAD database, including 14,827 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 0.11 (1125 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13702 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX15	NM_001140.5	c.808-94C>T		intron_variant		ENST00000293761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000293761.8	c.808-94C>T		intron_variant		1	NM_001140.5	P1
ALOX15	ENST00000570836.6	c.808-94C>T		intron_variant		2		P1
ALOX15	ENST00000574640.1	c.691-94C>T		intron_variant		2
ALOX15	ENST00000576572.1	n.399-94C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16520 AN: 152058 Hom.: 1124 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.142 AC: 175329 AN: 1236986 Hom.: 13702 AF XY: 0.140 AC XY: 84723 AN XY: 605274

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.000607

Gnomad4 SAS exome AF: 0.0644

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.109 AC: 16525 AN: 152176 Hom.: 1125 Cov.: 32 AF XY: 0.106 AC XY: 7893 AN XY: 74400

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.133

Alfa AF: 0.120 Hom.: 217

Bravo AF: 0.106

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	13
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11078527; hg19: chr17-4540647;