17-4632019-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

48 publications found

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 Gene-Disease associations (from GenCC):

pregnancy loss, recurrent, susceptibility
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ALOX15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ALOX15	NM_001140.5 link	c.1679C>T	p.Thr560Met	missense_variant	Exon 13 of 14	ENST00000293761.8	NP_001131.3	P16050-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALOX15	ENST00000293761.8 link	c.1679C>T	p.Thr560Met	missense_variant	Exon 13 of 14	1	NM_001140.5	ENSP00000293761.3	P16050-1
ALOX15	ENST00000570836.6 link	c.1679C>T	p.Thr560Met	missense_variant	Exon 14 of 15	2		ENSP00000458832.1	P16050-1
ALOX15	ENST00000574640.1 link	c.1562C>T	p.Thr521Met	missense_variant	Exon 13 of 14	2		ENSP00000460483.1	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

GnomAD2 exomes

AF:

0.0274

AC:

6861

AN:

250268

AF XY:

0.0235

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 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

African (AFR)

AF:

0.00335

AC:

112

AN:

33478

American (AMR)

AF:

0.113

AC:

5035

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00705

AC:

184

AN:

26086

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00974

AC:

839

AN:

86116

European-Finnish (FIN)

AF:

0.00782

AC:

416

AN:

53182

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0198

AC:

22038

AN:

1111756

Other (OTH)

AF:

0.0167

AC:

1006

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1789

3578

5368

7157

8946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0169

AC:

2579

AN:

152292

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1242

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00486

AC:

202

AN:

41572

American (AMR)

AF:

0.0643

AC:

984

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00808

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00895

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0173

AC:

1177

AN:

68022

Other (OTH)

AF:

0.0147

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

136

272

408

544

680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0168

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Asthma, nasal polyps, and aspirin intolerance

Benign:1

Mar 26, 2019

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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;.

PhyloP100

3.2

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over