Variant chr2-28525298-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153021.5(PLB1):c.275A>G(p.Lys92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,690 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0017 ( 40 hom. )

Consequence

PLB1
NM_153021.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

PLB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038392842).

BP6

Variant 2-28525298-A-G is Benign according to our data. Variant chr2-28525298-A-G is described in ClinVar as [Benign]. Clinvar id is 740634.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLB1	NM_153021.5 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	5/58	ENST00000327757.10
PLB1	NM_001170585.2 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	5/57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000327757.10 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	5/58	1	NM_153021.5	P1	Q6P1J6-1
PLB1	ENST00000422425.6 linkuse as main transcript	c.275A>G	p.Lys92Arg	missense_variant	5/57	1			Q6P1J6-3
PLB1	ENST00000404858.5 linkuse as main transcript	c.272A>G	p.Lys91Arg	missense_variant	5/57	1
PLB1	ENST00000416713.5 linkuse as main transcript	c.107A>G	p.Lys36Arg	missense_variant	5/11	5

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

405

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00366

AC:

918

AN:

251020

Hom.:

AF XY:

0.00321

AC XY:

435

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00174

AC:

2550

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1202

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00310

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152300

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000686

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00347

AC:

421

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0073

.;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.70, 0.013

.;P;B

Vest4

0.23, 0.20

MVP

0.048

MPC

0.048

ClinPred

0.029

GERP RS

2.0

Varity_R

0.064

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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