rs8179071

Positions:

chr15-89667102-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002666.5(PLIN1):c.1043C>T(p.Ser348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,084 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 14 hom., cov: 33)

Exomes 𝑓: 0.011 ( 138 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.13

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]

PLIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004059106).

BP6

Variant 15-89667102-G-A is Benign according to our data. Variant chr15-89667102-G-A is described in ClinVar as [Benign]. Clinvar id is 129969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89667102-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00696 (1060/152286) while in subpopulation SAS AF= 0.0393 (190/4832). AF 95% confidence interval is 0.0347. There are 14 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1060 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.1043C>T	p.Ser348Leu	missense_variant	8/9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2 linkuse as main transcript	c.1043C>T	p.Ser348Leu	missense_variant	8/9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PLIN1	ENST00000300055.10 linkuse as main transcript	c.1043C>T	p.Ser348Leu	missense_variant	8/9	1	NM_002666.5	ENSP00000300055	P1
PLIN1	ENST00000430628.2 linkuse as main transcript	c.1043C>T	p.Ser348Leu	missense_variant	8/9	5		ENSP00000402167	P1
PLIN1	ENST00000560330.1 linkuse as main transcript	c.119C>T	p.Ser40Leu	missense_variant	2/3	5		ENSP00000453426

Frequencies

GnomAD3 genomes

AF:

0.00698

AC:

1062

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00979

AC:

2461

AN:

251320

Hom.:

AF XY:

0.0115

AC XY:

1563

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0349

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.0112

AC:

16352

AN:

1461798

Hom.:

138

Cov.:

AF XY:

0.0118

AC XY:

8593

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00823

GnomAD4 genome

AF:

0.00696

AC:

1060

AN:

152286

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

529

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0393

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00898

Hom.:

Bravo

AF:

0.00619

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.0107

AC:

1299

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00936

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 31, 2014

- -

Monogenic diabetes

Benign:1

Benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Aug 10, 2018

ACMG criteria: BA1 (3.5% in gnomAD SA pop), BS2 (206 controls and 172 cases in T2DM) [REVEL 0.224, PP3 (5 predictors), BP4 (5 predictors)= conflicting evidence, not using]= benign -

PLIN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

T;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.66

.;T;D

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

M;.;M

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.26

MPC

0.18

ClinPred

0.020

GERP RS

5.3

Varity_R

0.32

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over