17-4633168-G-C

Variant names:

• chr17-4633168-G-C
• rs144526853
• NM_001140.5:c.1396C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001140.5(ALOX15):​c.1396C>G​(p.Arg466Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1396C>G	p.Arg466Gly	missense_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.1396C>G	p.Arg466Gly	missense_variant	Exon 10 of 14	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1396C>G	p.Arg466Gly	missense_variant	Exon 11 of 15	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1279C>G	p.Arg427Gly	missense_variant	Exon 10 of 14	2		ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;D;.
Eigen	Benign	0.079
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.6	.;D;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.028	.;D;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.35
MVP		0.88
MPC		0.29
ClinPred		0.98	D
GERP RS		1.4
Varity_R		0.78
gMVP		0.30

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: rs144526853; hg19: chr17-4536463;