chr17-8039274-A-G

Position:

chr17-8039274-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001141.3(ALOX15B):c.119A>G(p.Asn40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,591,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B links:

ALOX15B (HGNC:):

ALOX15B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity LX15B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043999523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15B	NM_001141.3 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/14	ENST00000380183.9	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/13		NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/12		NP_001034220.1	O15296-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9 linkuse as main transcript	c.119A>G	p.Asn40Ser	missense_variant	1/14	1	NM_001141.3	ENSP00000369530.4		O15296-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.00000438

AC:

AN:

228296

Hom.:

AF XY:

0.00000818

AC XY:

AN XY:

122240

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000970

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1439214

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000234

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:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.119A>G (p.N40S) alteration is located in exon 1 (coding exon 1) of the ALOX15B gene. This alteration results from a A to G substitution at nucleotide position 119, causing the asparagine (N) at amino acid position 40 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.71

DANN

Benign

0.92

DEOGEN2

Benign

0.0043

T;T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.044

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

N;.;N;.

REVEL

Benign

0.021

Sift

Benign

0.53

T;.;T;.

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0050

B;.;B;B

Vest4

0.084

MutPred

0.36

Gain of phosphorylation at N40 (P = 0.032);Gain of phosphorylation at N40 (P = 0.032);Gain of phosphorylation at N40 (P = 0.032);Gain of phosphorylation at N40 (P = 0.032);

MVP

0.49

MPC

0.12

ClinPred

0.034

GERP RS

0.44

Varity_R

0.15

gMVP

0.15

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

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