2-28529756-G-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_153021.5(PLB1):c.445G>T(p.Val149Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00144 in 1,614,106 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0080 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00076 ( 10 hom. )
Consequence
PLB1
NM_153021.5 missense
NM_153021.5 missense
Scores
1
8
7
Clinical Significance
Conservation
PhyloP100: 4.45
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005537182).
BP6
?
Variant 2-28529756-G-T is Benign according to our data. Variant chr2-28529756-G-T is described in ClinVar as [Benign]. Clinvar id is 767788.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00801 (1220/152238) while in subpopulation AFR AF= 0.0281 (1167/41530). AF 95% confidence interval is 0.0268. There are 21 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLB1 | NM_153021.5 | c.445G>T | p.Val149Leu | missense_variant | 8/58 | ENST00000327757.10 | |
PLB1 | NM_001170585.2 | c.445G>T | p.Val149Leu | missense_variant | 8/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLB1 | ENST00000327757.10 | c.445G>T | p.Val149Leu | missense_variant | 8/58 | 1 | NM_153021.5 | P1 | |
PLB1 | ENST00000422425.6 | c.445G>T | p.Val149Leu | missense_variant | 8/57 | 1 | |||
PLB1 | ENST00000404858.5 | c.442G>T | p.Val148Leu | missense_variant | 8/57 | 1 | |||
PLB1 | ENST00000416713.5 | c.277G>T | p.Val93Leu | missense_variant | 8/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00802 AC: 1220AN: 152120Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00229 AC: 577AN: 251418Hom.: 11 AF XY: 0.00182 AC XY: 247AN XY: 135882
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GnomAD4 exome AF: 0.000757 AC: 1106AN: 1461868Hom.: 10 Cov.: 33 AF XY: 0.000671 AC XY: 488AN XY: 727240
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GnomAD4 genome ? AF: 0.00801 AC: 1220AN: 152238Hom.: 21 Cov.: 32 AF XY: 0.00758 AC XY: 564AN XY: 74444
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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 | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.40, 1.0
.;B;D
Vest4
0.65, 0.68
MutPred
0.38
.;Gain of ubiquitination at K153 (P = 0.123);Gain of ubiquitination at K153 (P = 0.123);
MVP
MPC
0.11
ClinPred
T
GERP RS
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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