chr15-89667032-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002666.5(PLIN1):c.1113T>C(p.Pro371Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,613,576 control chromosomes in the GnomAD database, including 116,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11091 hom., cov: 33)

Exomes 𝑓: 0.38 ( 105711 hom. )

Consequence

PLIN1
NM_002666.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.85

Publications

56 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 15-89667032-A-G is Benign according to our data. Variant chr15-89667032-A-G is described in ClinVar as Benign. ClinVar VariationId is 129970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.1113T>C	p.Pro371Pro	synonymous_variant	Exon 8 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.1113T>C	p.Pro371Pro	synonymous_variant	Exon 8 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 link	c.1113T>C	p.Pro371Pro	synonymous_variant	Exon 8 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.1113T>C	p.Pro371Pro	synonymous_variant	Exon 8 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.123+66T>C		intron_variant	Intron 2 of 2	5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57550

AN:

151992

Hom.:

11100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.530

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.411

GnomAD2 exomes

AF:

0.379

AC:

94980

AN:

250832

AF XY:

0.387

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.377

AC:

551566

AN:

1461466

Hom.:

105711

Cov.:

AF XY:

0.382

AC XY:

277840

AN XY:

727038

show subpopulations

African (AFR)

AF:

0.383

AC:

12818

AN:

33478

American (AMR)

AF:

0.341

AC:

15238

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

10406

AN:

26132

East Asian (EAS)

AF:

0.276

AC:

10938

AN:

39694

South Asian (SAS)

AF:

0.516

AC:

44497

AN:

86236

European-Finnish (FIN)

AF:

0.340

AC:

18182

AN:

53404

Middle Eastern (MID)

AF:

0.436

AC:

2503

AN:

5738

European-Non Finnish (NFE)

AF:

0.372

AC:

413866

AN:

1111708

Other (OTH)

AF:

0.383

AC:

23118

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

21006

42012

63018

84024

105030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13136

26272

39408

52544

65680

<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:

0.378

AC:

57562

AN:

152110

Hom.:

11091

Cov.:

AF XY:

0.377

AC XY:

28049

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.387

AC:

16091

AN:

41532

American (AMR)

AF:

0.362

AC:

5541

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1377

AN:

3464

East Asian (EAS)

AF:

0.281

AC:

1444

AN:

5146

South Asian (SAS)

AF:

0.529

AC:

2552

AN:

4826

European-Finnish (FIN)

AF:

0.344

AC:

3640

AN:

10594

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25588

AN:

67936

Other (OTH)

AF:

0.405

AC:

856

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1918

3835

5753

7670

9588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.373

Hom.:

5398

Bravo

AF:

0.375

Asia WGS

AF:

0.408

AC:

1417

AN:

3478

EpiCase

AF:

0.387

EpiControl

AF:

0.390

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

- -

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

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.025

(source)

DANN

Benign

0.36

PhyloP100

-3.9

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