Genetic Variant ALOX15B:p.Arg90Cys (chr17-8039506-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001141.3(ALOX15B):c.268C>T(p.Arg90Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000803 in 1,570,012 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.121

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2537794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15B	NM_001141.3 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 14	ENST00000380183.9	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 13		NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 12		NP_001034220.1	O15296-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 14	1	NM_001141.3	ENSP00000369530.4		O15296-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000407

AC:

AN:

171830

Hom.:

AF XY:

0.0000421

AC XY:

AN XY:

95040

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:

0.0000991

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000811

AC:

115

AN:

1417932

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

702758

show subpopulations

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:

0.000104

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000595

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00000855

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.268C>T (p.R90C) alteration is located in exon 2 (coding exon 2) of the ALOX15B gene. This alteration results from a C to T substitution at nucleotide position 268, causing the arginine (R) at amino acid position 90 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;.;.

Eigen

Benign

0.0079

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.7

M;.;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.0

D;.;D;.

REVEL

Benign

0.23

Sift

Uncertain

0.018

D;.;D;.

Sift4G

Uncertain

0.025

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.47

MVP

0.38

MPC

0.74

ClinPred

0.87

GERP RS

0.79

Varity_R

0.30

gMVP

0.42

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