rs150004289
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002666.5(PLIN1):c.245C>T(p.Thr82Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00228 in 1,563,422 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 5 hom. )
Consequence
PLIN1
NM_002666.5 missense
NM_002666.5 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 5.73
Genes affected
PLIN1 (HGNC:9076): (perilipin 1) The protein encoded by this gene coats lipid storage droplets in adipocytes, thereby protecting them until they can be broken down by hormone-sensitive lipase. The encoded protein is the major cAMP-dependent protein kinase substrate in adipocytes and, when unphosphorylated, may play a role in the inhibition of lipolysis. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.02043277).
BP6
?
Variant 15-89673215-G-A is Benign according to our data. Variant chr15-89673215-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 393440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89673215-G-A is described in Lovd as [Likely_benign]. Variant chr15-89673215-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00153 (233/152256) while in subpopulation NFE AF= 0.00253 (172/68016). AF 95% confidence interval is 0.00222. There are 2 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 234 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLIN1 | NM_002666.5 | c.245C>T | p.Thr82Ile | missense_variant | 3/9 | ENST00000300055.10 | |
PLIN1 | NM_001145311.2 | c.245C>T | p.Thr82Ile | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLIN1 | ENST00000300055.10 | c.245C>T | p.Thr82Ile | missense_variant | 3/9 | 1 | NM_002666.5 | P1 | |
PLIN1 | ENST00000430628.2 | c.245C>T | p.Thr82Ile | missense_variant | 3/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00154 AC: 234AN: 152138Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00138 AC: 243AN: 175882Hom.: 0 AF XY: 0.00155 AC XY: 145AN XY: 93812
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GnomAD4 exome AF: 0.00236 AC: 3330AN: 1411166Hom.: 5 Cov.: 32 AF XY: 0.00226 AC XY: 1576AN XY: 697590
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GnomAD4 genome ? AF: 0.00153 AC: 233AN: 152256Hom.: 2 Cov.: 33 AF XY: 0.00132 AC XY: 98AN XY: 74438
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76
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Monogenic diabetes Benign:1
Benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | May 17, 2016 | ACMG Criteria: PP3, BS1 (ExAC), BS2 (ExAC), BP4 - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | PLIN1: BS1 - |
PLIN1-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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