NM_002666.5:c.692G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002666.5(PLIN1):c.692G>T(p.Arg231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,613,954 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 15 hom., cov: 31)

Exomes 𝑓: 0.00076 ( 17 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.46

Publications

4 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 -16 ACMG points.

BP6

Variant 15-89669579-C-A is Benign according to our data. Variant chr15-89669579-C-A is described in ClinVar as Benign. ClinVar VariationId is 393438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0077 (1172/152226) while in subpopulation AFR AF = 0.0267 (1108/41530). AF 95% confidence interval is 0.0254. There are 15 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.692G>T	p.Arg231Leu	missense_variant	Exon 6 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.692G>T	p.Arg231Leu	missense_variant	Exon 6 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10 link	c.692G>T	p.Arg231Leu	missense_variant	Exon 6 of 9	1	NM_002666.5	ENSP00000300055.5		O60240
PLIN1	ENST00000430628.2 link	c.692G>T	p.Arg231Leu	missense_variant	Exon 6 of 9	5		ENSP00000402167.2		O60240

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1169

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00189

AC:

475

AN:

251272

AF XY:

0.00138

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000762

AC:

1114

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000715

AC XY:

520

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0252

AC:

845

AN:

33480

American (AMR)

AF:

0.00152

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111948

Other (OTH)

AF:

0.00215

AC:

130

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00770

AC:

1172

AN:

152226

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0267

AC:

1108

AN:

41530

American (AMR)

AF:

0.00307

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68002

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

114

171

228

285

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:

0.00191

Hom.:

Bravo

AF:

0.00847

ESP6500AA

AF:

0.0255

AC:

112

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00244

AC:

296

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Monogenic diabetes

Benign:1

Feb 08, 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 0.073 + 7 predictors), BP5 (found in case with alternate cause), BA1 (2.5% MAF in gnomAD African)= benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.73

.;T

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

M;M

PhyloP100

-2.5

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.073

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

0.76

P;P

Vest4

0.41

MVP

0.055

MPC

0.059

ClinPred

0.053

GERP RS

-4.7

Varity_R

0.23

gMVP

0.39

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.45

Position offset: -14

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