rs770087312

Variant names:

• chr17-4631626-C-G
• rs770087312
• NM_001140.5:c.1963G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-4631626-C-G
• chr17-4631626-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001140.5(ALOX15):​c.1963G>C​(p.Val655Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030937374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1963G>C	p.Val655Leu	missense_variant	Exon 14 of 14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1963G>C	p.Val655Leu	missense_variant	Exon 14 of 14	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1963G>C	p.Val655Leu	missense_variant	Exon 15 of 15	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1846G>C	p.Val616Leu	missense_variant	Exon 14 of 14	2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.061
DANN	Benign	0.59
DEOGEN2	Benign	0.094	T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.034	.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.3	N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.14	.;N;.
REVEL	Benign	0.013
Sift	Benign	0.71	.;T;.
Sift4G	Benign	0.83	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.026
MVP		0.26
MPC		0.17
ClinPred		0.028	T
GERP RS		-5.2
Varity_R		0.043
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs770087312; hg19: chr17-4534921;