rs145476436

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002666.5(PLIN1):c.814G>A(p.Val272Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,564,906 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 10 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.59

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008209467).

BP6

Variant 15-89667751-C-T is Benign according to our data. Variant chr15-89667751-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 393437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.814G>A	p.Val272Met	missense_variant	Exon 7 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.814G>A	p.Val272Met	missense_variant	Exon 7 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 link	c.814G>A	p.Val272Met	missense_variant	Exon 7 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.814G>A	p.Val272Met	missense_variant	Exon 7 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.-111G>A		upstream_gene_variant		5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00177

AC:

303

AN:

170880

Hom.:

AF XY:

0.00168

AC XY:

152

AN XY:

90514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000354

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000524

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.000680

AC:

960

AN:

1412668

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

483

AN XY:

697878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.0263

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.000828

AC:

126

AN:

152238

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.000971

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00152

AC:

ExAC

AF:

0.000877

AC:

102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Monogenic diabetes

Benign:1

Jun 23, 2015

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria: BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.095

T;T

Polyphen

0.99

D;D

Vest4

0.37

MVP

0.19

MPC

0.17

ClinPred

0.063

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.94

Varity_R

0.13

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over