15-89669998-G-C

Position:

chr15-89669998-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002666.5(PLIN1):c.580C>G(p.Pro194Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,611,936 control chromosomes in the GnomAD database, including 768,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70682 hom., cov: 32)

Exomes 𝑓: 0.98 ( 697363 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.508

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=8.6493344E-7).

BP6

Variant 15-89669998-G-C is Benign according to our data. Variant chr15-89669998-G-C is described in ClinVar as [Benign]. Clinvar id is 129973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89669998-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.580C>G	p.Pro194Ala	missense_variant	5/9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 linkuse as main transcript	c.580C>G	p.Pro194Ala	missense_variant	5/9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10 linkuse as main transcript	c.580C>G	p.Pro194Ala	missense_variant	5/9	1	NM_002666.5	ENSP00000300055.5		O60240
PLIN1	ENST00000430628.2 linkuse as main transcript	c.580C>G	p.Pro194Ala	missense_variant	5/9	5		ENSP00000402167.2		O60240

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146288

AN:

152106

Hom.:

70636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.974

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.951

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.956

GnomAD3 exomes

AF:

0.929

AC:

228090

AN:

245494

Hom.:

107106

AF XY:

0.936

AC XY:

124531

AN XY:

133104

show subpopulations

Gnomad AFR exome

AF:

0.975

Gnomad AMR exome

AF:

0.772

Gnomad ASJ exome

AF:

0.996

Gnomad EAS exome

AF:

0.737

Gnomad SAS exome

AF:

0.904

Gnomad FIN exome

AF:

0.952

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.952

GnomAD4 exome

AF:

0.975

AC:

1423753

AN:

1459712

Hom.:

697363

Cov.:

AF XY:

0.974

AC XY:

707623

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.976

Gnomad4 AMR exome

AF:

0.783

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

0.709

Gnomad4 SAS exome

AF:

0.910

Gnomad4 FIN exome

AF:

0.953

Gnomad4 NFE exome

AF:

0.998

Gnomad4 OTH exome

AF:

0.970

GnomAD4 genome

AF:

0.962

AC:

146392

AN:

152224

Hom.:

70682

Cov.:

AF XY:

0.955

AC XY:

71027

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.974

Gnomad4 AMR

AF:

0.859

Gnomad4 ASJ

AF:

0.997

Gnomad4 EAS

AF:

0.743

Gnomad4 SAS

AF:

0.896

Gnomad4 FIN

AF:

0.951

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.951

Alfa

AF:

0.984

Hom.:

43081

Bravo

AF:

0.953

TwinsUK

AF:

0.999

AC:

3704

ALSPAC

AF:

0.998

AC:

3848

ESP6500AA

AF:

0.973

AC:

4283

ESP6500EA

AF:

0.998

AC:

8577

ExAC

AF:

0.937

AC:

113692

EpiCase

AF:

0.999

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 25529448) -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PLIN1-related familial partial lipodystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.062

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.66

.;T

MetaRNN

Benign

8.6e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.028

Sift

Benign

0.71

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0020

B;B

Vest4

0.068

MPC

0.025

ClinPred

0.00097

GERP RS

3.1

Varity_R

0.027

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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