rs58361219

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.812C>T(p.Ala271Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,563,944 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 4 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.70

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051777065).

BP6

Variant 15-89667753-G-A is Benign according to our data. Variant chr15-89667753-G-A is described in ClinVar as Benign. ClinVar VariationId is 129974.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 = 0.00575 (876/152318) while in subpopulation AFR AF = 0.0202 (840/41572). AF 95% confidence interval is 0.0191. There are 9 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 876 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2 link	c.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PLIN1	ENST00000300055.10 link	c.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2 link	c.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9	5		ENSP00000402167.2
PLIN1	ENST00000560330.1 link	c.-113C>T		upstream_gene_variant		5		ENSP00000453426.1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00155

AC:

262

AN:

169310

AF XY:

0.00128

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.000514

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.000214

GnomAD4 exome

AF:

0.000677

AC:

956

AN:

1411626

Hom.:

Cov.:

AF XY:

0.000611

AC XY:

426

AN XY:

697268

show subpopulations

African (AFR)

AF:

0.0239

AC:

779

AN:

32596

American (AMR)

AF:

0.000578

AC:

AN:

36310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25232

East Asian (EAS)

AF:

0.00

AC:

AN:

37436

South Asian (SAS)

AF:

0.000274

AC:

AN:

80226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49230

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.0000598

AC:

AN:

1086248

Other (OTH)

AF:

0.00107

AC:

AN:

58640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00575

AC:

876

AN:

152318

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0202

AC:

840

AN:

41572

American (AMR)

AF:

0.00118

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00311

Hom.:

Bravo

AF:

0.00670

ESP6500AA

AF:

0.0167

AC:

ESP6500EA

AF:

0.000702

AC:

ExAC

AF:

0.00145

AC:

168

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

Monogenic diabetes

Benign:1

Oct 12, 2018

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 0.063 + 9 predictors), BA1 (2% in gnomAD African), BS2 (33 cases and 31 controls in T2DM): benign -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.065

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.66

.;T

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.8

N;N

PhyloP100

1.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.063

Sift

Benign

0.40

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.085

MVP

0.014

MPC

0.024

ClinPred

0.0025

GERP RS

2.3

PromoterAI

0.0016

Neutral

(source)

Varity_R

0.030

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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