2-28496125-G-A

Position:

chr2-28496125-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_153021.5(PLB1):c.11G>A(p.Arg4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PLB1
NM_153021.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.83

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023959875).

BP6

Variant 2-28496125-G-A is Benign according to our data. Variant chr2-28496125-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3214316.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLB1	NM_153021.5 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/58	ENST00000327757.10
PLB1	NM_001170585.2 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000327757.10 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/58	1	NM_153021.5	P1	Q6P1J6-1
PLB1	ENST00000422425.6 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/57	1			Q6P1J6-3
PLB1	ENST00000404858.5 linkuse as main transcript	c.8G>A	p.Arg3Gln	missense_variant	1/57	1
PLB1	ENST00000416713.5 linkuse as main transcript	c.-113-20683G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251096

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0020

DANN

Benign

0.60

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.32

N;N

REVEL

Benign

0.022

Sift

Benign

0.41

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;B

Vest4

0.092

MutPred

0.28

Loss of methylation at R4 (P = 0.0111);Loss of methylation at R4 (P = 0.0111);

MVP

0.16

MPC

0.045

ClinPred

0.036

GERP RS

-9.2

Varity_R

0.018

gMVP

0.21

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