Variant 17-4633287-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001140.5(ALOX15):c.1277T>G(p.Val426Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ALOX15
NM_001140.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.57

Variant links:

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]

ALOX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0449636).

BP6

Variant 17-4633287-A-C is Benign according to our data. Variant chr17-4633287-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 742473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5 linkuse as main transcript	c.1277T>G	p.Val426Gly	missense_variant	10/14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8 linkuse as main transcript	c.1277T>G	p.Val426Gly	missense_variant	10/14	1	NM_001140.5	ENSP00000293761	P1	P16050-1
ALOX15	ENST00000570836.6 linkuse as main transcript	c.1277T>G	p.Val426Gly	missense_variant	11/15	2		ENSP00000458832	P1	P16050-1
ALOX15	ENST00000574640.1 linkuse as main transcript	c.1160T>G	p.Val387Gly	missense_variant	10/14	2		ENSP00000460483		P16050-2

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251212

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000578

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00212

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000805

Hom.:

Bravo

AF:

0.000608

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;D;.

Eigen

Benign

0.10

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.1

.;D;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

.;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.43

MVP

0.85

MPC

0.82

ClinPred

0.29

GERP RS

3.8

Varity_R

0.78

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over