rs146385147

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002666.5(PLIN1):​c.1139C>T​(p.Ala380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,996 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0057 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

1
5
12

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.27
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008093566).
BP6
Variant 15-89667006-G-A is Benign according to our data. Variant chr15-89667006-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 129967.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}. Variant chr15-89667006-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00572 (871/152330) while in subpopulation AFR AF= 0.0198 (822/41570). AF 95% confidence interval is 0.0187. There are 10 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 871 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLIN1NM_002666.5 linkuse as main transcriptc.1139C>T p.Ala380Val missense_variant 8/9 ENST00000300055.10 NP_002657.3 O60240
PLIN1NM_001145311.2 linkuse as main transcriptc.1139C>T p.Ala380Val missense_variant 8/9 NP_001138783.1 O60240

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLIN1ENST00000300055.10 linkuse as main transcriptc.1139C>T p.Ala380Val missense_variant 8/91 NM_002666.5 ENSP00000300055.5 O60240
PLIN1ENST00000430628.2 linkuse as main transcriptc.1139C>T p.Ala380Val missense_variant 8/95 ENSP00000402167.2 O60240
PLIN1ENST00000560330.1 linkuse as main transcriptc.123+92C>T intron_variant 5 ENSP00000453426.1 H0YM16

Frequencies

GnomAD3 genomes
AF:
0.00571
AC:
869
AN:
152210
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0198
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00144
AC:
361
AN:
251128
Hom.:
1
AF XY:
0.000943
AC XY:
128
AN XY:
135772
show subpopulations
Gnomad AFR exome
AF:
0.0198
Gnomad AMR exome
AF:
0.000839
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000581
AC:
849
AN:
1461666
Hom.:
7
Cov.:
32
AF XY:
0.000488
AC XY:
355
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0209
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00126
GnomAD4 genome
AF:
0.00572
AC:
871
AN:
152330
Hom.:
10
Cov.:
33
AF XY:
0.00571
AC XY:
425
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0198
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000872
Hom.:
2
Bravo
AF:
0.00652
ESP6500AA
AF:
0.0189
AC:
83
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00164
AC:
199
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 20, 2018- -
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoSep 05, 2013- -
Monogenic diabetes Benign:1
Benign, criteria provided, single submitterresearchPersonalized Diabetes Medicine Program, University of Maryland School of MedicineJan 25, 2019ACMG criteria: BA1 (2.1% MAF in gnomAD Africans), BS2 (66 cases and 47 controls in T2DM)= benign (REVEL 0.199 + PP3/3 predictors + BP4/7 predictors: conflicting evidence, not using) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.68
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.067
T;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.82
.;T
MetaRNN
Benign
0.0081
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M
MutationTaster
Benign
0.72
N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
0.39
N;N
REVEL
Benign
0.20
Sift
Benign
0.23
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.10
MVP
0.25
MPC
0.12
ClinPred
0.037
T
GERP RS
5.1
Varity_R
0.063
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs146385147; hg19: chr15-90210237; API