rs8179071

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.1043C>T(p.Ser348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,084 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 14 hom., cov: 33)

Exomes 𝑓: 0.011 ( 138 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.13

Publications

10 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: DEFINITIVE, STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

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=0.004059106).

BP6

Variant 15-89667102-G-A is Benign according to our data. Variant chr15-89667102-G-A is described in ClinVar as Benign. ClinVar VariationId is 129969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00696 (1060/152286) while in subpopulation SAS AF = 0.0393 (190/4832). AF 95% confidence interval is 0.0347. There are 14 homozygotes in GnomAd4. There are 529 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1060 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.1043C>T	p.Ser348Leu	missense	Exon 8 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1043C>T	p.Ser348Leu	missense	Exon 8 of 9	NP_001138783.1	O60240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.1043C>T	p.Ser348Leu	missense	Exon 8 of 9	ENSP00000300055.5	O60240
PLIN1	ENST00000896664.1		c.1151C>T	p.Ser384Leu	missense	Exon 8 of 9	ENSP00000566723.1
PLIN1	ENST00000896666.1		c.1073C>T	p.Ser358Leu	missense	Exon 8 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes

AF:

0.00698

AC:

1062

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00979

AC:

2461

AN:

251320

AF XY:

0.0115

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.0112

AC:

16352

AN:

1461798

Hom.:

138

Cov.:

AF XY:

0.0118

AC XY:

8593

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

33480

American (AMR)

AF:

0.00371

AC:

166

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0348

AC:

3004

AN:

86252

European-Finnish (FIN)

AF:

0.00290

AC:

155

AN:

53376

Middle Eastern (MID)

AF:

0.00244

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0111

AC:

12390

AN:

1111994

Other (OTH)

AF:

0.00823

AC:

497

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1007

2014

3021

4028

5035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.00696

AC:

1060

AN:

152286

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

529

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41566

American (AMR)

AF:

0.00320

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.0393

AC:

190

AN:

4832

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

702

AN:

68006

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

111

167

222

278

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:

0.00905

Hom.:

Bravo

AF:

0.00619

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.0107

AC:

1299

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00936

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Monogenic diabetes (1)

not specified (1)

PLIN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

PhyloP100

3.1

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.26

MPC

0.18

ClinPred

0.020

GERP RS

5.3

Varity_R

0.32

gMVP

0.34

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over