rs2304796

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1119C>T(p.Val373Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,584 control chromosomes in the GnomAD database, including 74,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5605 hom., cov: 33)

Exomes 𝑓: 0.30 ( 69181 hom. )

Consequence

PLIN1
NM_002666.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.15

Publications

19 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=-0.81).

BP6

Variant 15-89667026-G-A is Benign according to our data. Variant chr15-89667026-G-A is described in ClinVar as Benign. ClinVar VariationId is 129971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.1119C>T	p.Val373Val	synonymous_variant	Exon 8 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.1119C>T	p.Val373Val	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.1119C>T	p.Val373Val	synonymous_variant	Exon 8 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.1119C>T	p.Val373Val	synonymous_variant	Exon 8 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.123+72C>T		intron_variant	Intron 2 of 2	5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39684

AN:

152028

Hom.:

5604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.284

AC:

71261

AN:

250828

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.304

AC:

444295

AN:

1461438

Hom.:

69181

Cov.:

AF XY:

0.309

AC XY:

224320

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.163

AC:

5450

AN:

33472

American (AMR)

AF:

0.187

AC:

8358

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

9454

AN:

26130

East Asian (EAS)

AF:

0.279

AC:

11082

AN:

39692

South Asian (SAS)

AF:

0.403

AC:

34760

AN:

86232

European-Finnish (FIN)

AF:

0.211

AC:

11254

AN:

53406

Middle Eastern (MID)

AF:

0.324

AC:

1859

AN:

5736

European-Non Finnish (NFE)

AF:

0.309

AC:

343614

AN:

1111684

Other (OTH)

AF:

0.306

AC:

18464

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18808

37615

56423

75230

94038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11272

22544

33816

45088

56360

<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:

0.261

AC:

39695

AN:

152146

Hom.:

5605

Cov.:

AF XY:

0.256

AC XY:

19076

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.175

AC:

7252

AN:

41532

American (AMR)

AF:

0.230

AC:

3523

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1217

AN:

3468

East Asian (EAS)

AF:

0.302

AC:

1554

AN:

5146

South Asian (SAS)

AF:

0.412

AC:

1988

AN:

4830

European-Finnish (FIN)

AF:

0.194

AC:

2053

AN:

10604

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21096

AN:

67950

Other (OTH)

AF:

0.274

AC:

579

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1534

3067

4601

6134

7668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.254

Hom.:

3063

Bravo

AF:

0.255

Asia WGS

AF:

0.326

AC:

1133

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.316

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.50

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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