Variant chr17-4632019-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001140.5(ALOX15):c.1679C>T(p.Thr560Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,613,394 control chromosomes in the GnomAD database, including 659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 47 hom., cov: 33)

Exomes 𝑓: 0.020 ( 612 hom. )

Consequence

ALOX15
NM_001140.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.21

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038241744).

BP6

Variant 17-4632019-G-A is Benign according to our data. Variant chr17-4632019-G-A is described in ClinVar as [Benign]. Clinvar id is 624559.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5 linkuse as main transcript	c.1679C>T	p.Thr560Met	missense_variant	13/14	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.1679C>T	p.Thr560Met	missense_variant	13/14	1	NM_001140.5	ENSP00000293761	P1	P16050-1
ALOX15	ENST00000570836.6 linkuse as main transcript	c.1679C>T	p.Thr560Met	missense_variant	14/15	2		ENSP00000458832	P1	P16050-1
ALOX15	ENST00000574640.1 linkuse as main transcript	c.1562C>T	p.Thr521Met	missense_variant	13/14	2		ENSP00000460483		P16050-2

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2578

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00487

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.00895

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0274

AC:

6861

AN:

250268

Hom.:

339

AF XY:

0.0235

AC XY:

3181

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.00630

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00969

Gnomad FIN exome

AF:

0.00794

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0203

AC:

29658

AN:

1461102

Hom.:

612

Cov.:

AF XY:

0.0194

AC XY:

14092

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.00335

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.00705

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00974

Gnomad4 FIN exome

AF:

0.00782

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0169

AC:

2579

AN:

152292

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1242

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0643

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.00895

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0213

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0167

AC:

144

ExAC

AF:

0.0229

AC:

2785

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0146

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Asthma, nasal polyps, and aspirin intolerance

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

D;D;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;D;D

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Pathogenic

3.3

M;M;.

MutationTaster

Benign

0.76

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.9

.;D;.

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.19

MPC

0.73

ClinPred

0.047

GERP RS

3.4

Varity_R

0.65

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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