dbSNP rs140623478: ALOX15B:p.Arg461Gln (chr17-8047001-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001141.3(ALOX15B):c.1382G>A(p.Arg461Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,614,084 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 23 hom. )

Consequence

ALOX15B
NM_001141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.838

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004040092).

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15B	NM_001141.3 link	c.1382G>A	p.Arg461Gln	missense_variant	Exon 10 of 14	ENST00000380183.9	NP_001132.2	O15296-1
ALOX15B	NM_001039130.2 link	c.1295G>A	p.Arg432Gln	missense_variant	Exon 9 of 13		NP_001034219.1	O15296-4
ALOX15B	NM_001039131.2 link	c.1295G>A	p.Arg432Gln	missense_variant	Exon 9 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.1382G>A	p.Arg461Gln	missense_variant	Exon 10 of 14	1	NM_001141.3	ENSP00000369530.4		O15296-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00352

AC:

885

AN:

251464

Hom.:

AF XY:

0.00419

AC XY:

570

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00235

AC:

3431

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

2004

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00627

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00168

AC:

256

AN:

152214

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00172

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00373

AC:

453

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00362

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Aug 07, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.9

DANN

Benign

0.93

DEOGEN2

Benign

0.037

T;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.68

T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.84

N;.;N;.

REVEL

Benign

0.13

Sift

Benign

0.55

T;.;T;.

Sift4G

Benign

0.80

T;T;T;T

Polyphen

0.047

B;.;B;B

Vest4

0.047

MVP

0.83

MPC

0.18

ClinPred

0.0088

GERP RS

-1.1

Varity_R

0.18

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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