dbSNP rs368311556: ALOX15B:p.Arg90Ser (chr17-8039506-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001141.3(ALOX15B):c.268C>A(p.Arg90Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,570,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.121

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017072976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX15B	NM_001141.3	MANE Select	c.268C>A	p.Arg90Ser	missense	Exon 2 of 14	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2		c.268C>A	p.Arg90Ser	missense	Exon 2 of 13	NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2		c.268C>A	p.Arg90Ser	missense	Exon 2 of 12	NP_001034220.1	O15296-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX15B	ENST00000380183.9	TSL:1 MANE Select	c.268C>A	p.Arg90Ser	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
ALOX15B	ENST00000380173.6	TSL:1	c.268C>A	p.Arg90Ser	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
ALOX15B	ENST00000573359.1	TSL:1	c.268C>A	p.Arg90Ser	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152080

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:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

171830

AF XY:

0.0000210

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000846

AC:

AN:

1417932

Hom.:

Cov.:

AF XY:

0.00000854

AC XY:

AN XY:

702758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32216

American (AMR)

AF:

0.00

AC:

AN:

40082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25382

East Asian (EAS)

AF:

0.00

AC:

AN:

36938

South Asian (SAS)

AF:

0.000122

AC:

AN:

82158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092594

Other (OTH)

AF:

0.00

AC:

AN:

58722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ExAC

AF:

0.0000342

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.8

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.73

M_CAP

Benign

0.0070

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PhyloP100

-0.12

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.090

REVEL

Benign

0.087

Sift

Benign

1.0

Sift4G

Benign

0.73

Polyphen

0.062

Vest4

0.19

MutPred

0.72

Gain of catalytic residue at W91 (P = 0.1544)

MVP

0.099

MPC

0.50

ClinPred

0.099

GERP RS

0.79

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.35

gMVP

0.36

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over