rs764803400

Variant names:

• chr17-4631670-C-A
• NM_001140.5:c.1919G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-4631670-C-A
• chr17-4631670-C-G
• chr17-4631670-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001140.5(ALOX15):​c.1919G>T​(p.Arg640Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R640Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1919G>T	p.Arg640Leu	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.1919G>T	p.Arg640Leu	missense_variant	Exon 14 of 14	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.1919G>T	p.Arg640Leu	missense_variant	Exon 15 of 15	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.1802G>T	p.Arg601Leu	missense_variant	Exon 14 of 14	2		ENSP00000460483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D;D;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Pathogenic	3.9	H;H;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.2	.;D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	.;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.49
MVP		0.88
MPC		0.79
ClinPred		0.94	D
GERP RS		3.0
Varity_R		0.60
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4534965;