17-4638309-C-T

Position:

• chr17-4638309-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000293761.8(ALOX15):​c.715G>A​(p.Val239Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (0 hom., cov: 20)
  • Exomes 𝑓: 0.028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALOX15 ENST00000293761.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056161582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.715G>A	p.Val239Met	missense_variant	6/14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.715G>A	p.Val239Met	missense_variant	6/14	1	NM_001140.5	ENSP00000293761	P1
ALOX15	ENST00000570836.6	c.715G>A	p.Val239Met	missense_variant	7/15	2		ENSP00000458832	P1
ALOX15	ENST00000574640.1	c.598G>A	p.Val200Met	missense_variant	6/14	2		ENSP00000460483
ALOX15	ENST00000576572.1	n.306G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 16008 AN: 82538 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.182

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0280 AC: 12590 AN: 449222 Hom.: 0 Cov.: 8 AF XY: 0.0262 AC XY: 6157 AN XY: 235064

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0872

Gnomad4 SAS exome AF: 0.00395

Gnomad4 FIN exome AF: 0.0377

Gnomad4 NFE exome AF: 0.0280

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.194 AC: 16011 AN: 82612 Hom.: 0 Cov.: 20 AF XY: 0.194 AC XY: 7845 AN XY: 40394

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0469 Hom.: 0

ExAC AF: 0.00233 AC: 116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.2
DANN	Benign	0.080
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.64	.;T;T
MetaRNN	Benign	0.0056	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.60	N;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	1.4	.;N;.
REVEL	Benign	0.012
Sift	Benign	1.0	.;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.095
MVP		0.18
MPC		0.18
ClinPred		0.00061	T
GERP RS		3.0
Varity_R		0.058
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs3892408; hg19: chr17-4541604; COSMIC: COSV53396176; COSMIC: COSV53396176;