chr2-28525298-A-G
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
NM_153021.5 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 1.21
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]
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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 GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLB1 | NM_153021.5 | c.275A>G | p.Lys92Arg | missense_variant | 5/58 | ENST00000327757.10 | |
PLB1 | NM_001170585.2 | c.275A>G | p.Lys92Arg | missense_variant | 5/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLB1 | ENST00000327757.10 | c.275A>G | p.Lys92Arg | missense_variant | 5/58 | 1 | NM_153021.5 | P1 | |
PLB1 | ENST00000422425.6 | c.275A>G | p.Lys92Arg | missense_variant | 5/57 | 1 | |||
PLB1 | ENST00000404858.5 | c.272A>G | p.Lys91Arg | missense_variant | 5/57 | 1 | |||
PLB1 | ENST00000416713.5 | c.107A>G | p.Lys36Arg | missense_variant | 5/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00266 AC: 405AN: 152182Hom.: 2 Cov.: 30
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GnomAD3 exomes AF: 0.00366 AC: 918AN: 251020Hom.: 10 AF XY: 0.00321 AC XY: 435AN XY: 135708
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GnomAD4 exome AF: 0.00174 AC: 2550AN: 1461390Hom.: 40 Cov.: 31 AF XY: 0.00165 AC XY: 1202AN XY: 726962
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GnomAD4 genome ? AF: 0.00266 AC: 405AN: 152300Hom.: 2 Cov.: 30 AF XY: 0.00384 AC XY: 286AN XY: 74474
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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 | Invitae | Apr 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.70, 0.013
.;P;B
Vest4
0.23, 0.20
MVP
MPC
0.048
ClinPred
T
GERP RS
Varity_R
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at