chr2-28541705-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PVS1_ModeratePM2BP6_Moderate
The NM_153021.5(PLB1):c.775-2A>C variant causes a splice acceptor change. The variant allele was found at a frequency of 0.000201 in 1,613,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
PLB1
NM_153021.5 splice_acceptor
NM_153021.5 splice_acceptor
Scores
2
4
1
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 4.11
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 Uncertain_significance. Variant got 2 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.023760566 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.8, offset of 4, new splice context is: ctgctcccttctcccggaAGcct. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-28541705-A-C is Benign according to our data. Variant chr2-28541705-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 781804.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 | c.775-2A>C | splice_acceptor_variant | ENST00000327757.10 | |||
PLB1 | NM_001170585.2 | c.808-2A>C | splice_acceptor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLB1 | ENST00000327757.10 | c.775-2A>C | splice_acceptor_variant | 1 | NM_153021.5 | P1 | |||
PLB1 | ENST00000404858.5 | c.804-2A>C | splice_acceptor_variant | 1 | |||||
PLB1 | ENST00000422425.6 | c.808-2A>C | splice_acceptor_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152158Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000332 AC: 83AN: 250234Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135256
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GnomAD4 exome AF: 0.000193 AC: 282AN: 1461014Hom.: 0 Cov.: 30 AF XY: 0.000202 AC XY: 147AN XY: 726858
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
GERP RS
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 34
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at