NM_001140.5:c.1417C>G

Variant names:

• chr17-4633147-G-C
• rs760167475
• NM_001140.5:c.1417C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001140.5(ALOX15):​c.1417C>G​(p.Arg473Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ALOX15 NM_001140.5 missense, splice_region
• Scores: Splicing: ADA: 0.004109
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37524998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1417C>G	p.Arg473Gly	missense_variant, splice_region_variant	Exon 10 of 14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1417C>G	p.Arg473Gly	missense_variant, splice_region_variant	Exon 10 of 14	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1417C>G	p.Arg473Gly	missense_variant, splice_region_variant	Exon 11 of 15	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1300C>G	p.Arg434Gly	missense_variant, splice_region_variant	Exon 10 of 14	2		ENSP00000460483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461462 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D;D;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.4	.;D;.
REVEL	Benign	0.089
Sift	Uncertain	0.0060	.;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.23
MVP		0.48
MPC		0.36
ClinPred		0.82	D
GERP RS		0.041
Varity_R		0.61
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0041
dbscSNV1_RF	Benign	0.076
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: rs760167475; hg19: chr17-4536442;