rs3892408

Variant names:

• chr17-4638309-C-A
• rs3892408
• NM_001140.5:c.715G>T
• ALOX15 p.Val239Leu

Your query was ambiguous. Multiple possible variants found:

• chr17-4638309-C-A
• chr17-4638309-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001140.5(ALOX15):​c.715G>T​(p.Val239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 20)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.118282735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	NM_001140.5	MANE Select	c.715G>T	p.Val239Leu	missense	Exon 6 of 14	NP_001131.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.715G>T	p.Val239Leu	missense	Exon 6 of 14	ENSP00000293761.3	P16050-1
	ALOX15	ENST00000570836.6	TSL:2	c.715G>T	p.Val239Leu	missense	Exon 7 of 15	ENSP00000458832.1	P16050-1
	ALOX15	ENST00000574640.1	TSL:2	c.598G>T	p.Val200Leu	missense	Exon 6 of 14	ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.070	N
PhyloP100		0.23
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.037
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.043	D
Varity_R		0.084
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3892408;

hg19: chr17-4541604;