rs111663599

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002666.5(PLIN1):c.466G>T(p.Val156Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,614,048 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 23 hom., cov: 32)

Exomes 𝑓: 0.011 ( 176 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.219

Publications

9 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=0.0034962893).

BP6

Variant 15-89670112-C-A is Benign according to our data. Variant chr15-89670112-C-A is described in ClinVar as Benign. ClinVar VariationId is 393439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0104 (1583/152340) while in subpopulation NFE AF = 0.0122 (828/68026). AF 95% confidence interval is 0.0115. There are 23 homozygotes in GnomAd4. There are 902 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1583 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.466G>T	p.Val156Leu	missense_variant	Exon 5 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.466G>T	p.Val156Leu	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.466G>T	p.Val156Leu	missense_variant	Exon 5 of 9	1	NM_002666.5	ENSP00000300055.5		O60240
PLIN1	ENST00000430628.2 link	c.466G>T	p.Val156Leu	missense_variant	Exon 5 of 9	5		ENSP00000402167.2		O60240

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1585

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0531

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.0125

AC:

3136

AN:

250760

AF XY:

0.0125

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0518

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0110

AC:

16084

AN:

1461708

Hom.:

176

Cov.:

AF XY:

0.0107

AC XY:

7764

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33474

American (AMR)

AF:

0.00465

AC:

208

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00268

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00107

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.0538

AC:

2870

AN:

53376

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0109

AC:

12160

AN:

1111930

Other (OTH)

AF:

0.00972

AC:

587

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

983

1966

2948

3931

4914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.0104

AC:

1583

AN:

152340

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

902

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41586

American (AMR)

AF:

0.00634

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0531

AC:

564

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

828

AN:

68026

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0113

Hom.:

Bravo

AF:

0.00691

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.0134

AC:

1622

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLIN1: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Monogenic diabetes

Benign:1

Feb 01, 2019

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG criteria: BP4 (REVEL 0.046 + 8 predictors), not using PP3 (2 predictors)), BA1 (5.3% in gnomAD EF, MAF 1.5% overall), BS2 (204 cases and 197 controls in type2diabetesgenetics.org)= benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

0.22

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.046

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.16

T;T

Polyphen

0.095

B;B

Vest4

0.090

MutPred

0.67

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MPC

0.028

ClinPred

0.011

GERP RS

0.41

Varity_R

0.10

gMVP

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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