15-89669998-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

38 publications found

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 Gene-Disease associations (from GenCC):

PLIN1-related familial partial lipodystrophy
Inheritance: AD Classification: STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

PLIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 129973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.580C>G	p.Pro194Ala	missense_variant	Exon 5 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.580C>G	p.Pro194Ala	missense_variant	Exon 5 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10 link	c.580C>G	p.Pro194Ala	missense_variant	Exon 5 of 9	1	NM_002666.5	ENSP00000300055.5		O60240
PLIN1	ENST00000430628.2 link	c.580C>G	p.Pro194Ala	missense_variant	Exon 5 of 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

GnomAD2 exomes

AF:

0.929

AC:

228090

AN:

245494

AF XY:

0.936

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 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

African (AFR)

AF:

0.976

AC:

32626

AN:

33444

American (AMR)

AF:

0.783

AC:

34769

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.996

AC:

26003

AN:

26102

East Asian (EAS)

AF:

0.709

AC:

28088

AN:

39638

South Asian (SAS)

AF:

0.910

AC:

78235

AN:

85938

European-Finnish (FIN)

AF:

0.953

AC:

50042

AN:

52532

Middle Eastern (MID)

AF:

0.994

AC:

5725

AN:

5762

European-Non Finnish (NFE)

AF:

0.998

AC:

1109766

AN:

1111546

Other (OTH)

AF:

0.970

AC:

58499

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1811

3621

5432

7242

9053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21616

43232

64848

86464

108080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.962

AC:

146392

AN:

152224

Hom.:

70682

Cov.:

AF XY:

0.955

AC XY:

71027

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.974

AC:

40446

AN:

41518

American (AMR)

AF:

0.859

AC:

13141

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3458

AN:

3470

East Asian (EAS)

AF:

0.743

AC:

3831

AN:

5154

South Asian (SAS)

AF:

0.896

AC:

4327

AN:

4830

European-Finnish (FIN)

AF:

0.951

AC:

10096

AN:

10614

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.998

AC:

67877

AN:

68022

Other (OTH)

AF:

0.951

AC:

2010

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

261

522

782

1043

1304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25529448) -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

0.51

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over