17-4633917-C-G

Variant names:

• chr17-4633917-C-G
• rs2515889
• NM_001140.5:c.1162-417G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001140.5(ALOX15):​c.1162-417G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,164 control chromosomes in the GnomAD database, including 58,238 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 0.87 (58238 hom., cov: 32)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 2 publications found

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]

ALOX15 Gene-Disease associations (from GenCC):

• pregnancy loss, recurrent, susceptibility

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1162-417G>C		intron_variant	Intron 8 of 13	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1162-417G>C		intron_variant	Intron 8 of 13	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1162-417G>C		intron_variant	Intron 9 of 14	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1045-417G>C		intron_variant	Intron 8 of 13	2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132931 AN: 152046 Hom.: 58196 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.850

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.874 AC: 133030 AN: 152164 Hom.: 58238 Cov.: 32 AF XY: 0.877 AC XY: 65242 AN XY: 74372

African (AFR) AF: 0.913 AC: 37900 AN: 41528

American (AMR) AF: 0.852 AC: 13023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3026 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5168 AN: 5176

South Asian (SAS) AF: 0.945 AC: 4556 AN: 4822

European-Finnish (FIN) AF: 0.880 AC: 9313 AN: 10582

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57276 AN: 67984

Other (OTH) AF: 0.851 AC: 1801 AN: 2116

Alfa AF: 0.834 Hom.: 2580

Bravo AF: 0.873

Asia WGS AF: 0.957 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.65
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2515889; hg19: chr17-4537212;