Genetic Variant PLIN1:p.Pro462Pro (chr15-89665766-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_002666.5(PLIN1):c.1386C>G(p.Pro462Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000089 in 1,123,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P462P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

PLIN1
NM_002666.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.973

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-89665766-G-C is Benign according to our data. Variant chr15-89665766-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033886.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.973 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.1386C>G	p.Pro462Pro	synonymous_variant	Exon 9 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.1386C>G	p.Pro462Pro	synonymous_variant	Exon 9 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 link	c.1386C>G	p.Pro462Pro	synonymous_variant	Exon 9 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.1386C>G	p.Pro462Pro	synonymous_variant	Exon 9 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.124-825C>G		intron_variant	Intron 2 of 2	5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.90e-7

AC:

AN:

1123252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22542

American (AMR)

AF:

0.00

AC:

AN:

8226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14174

East Asian (EAS)

AF:

0.00

AC:

AN:

25528

South Asian (SAS)

AF:

0.00

AC:

AN:

32574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3006

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

948366

Other (OTH)

AF:

0.00

AC:

AN:

44718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLIN1-related disorder

Benign:1

Apr 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.9

(source)

DANN

Benign

0.75

PhyloP100

-0.97

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over