Variant rs2304796 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002666.5(PLIN1):c.1119C>T(p.Val373=) 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

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 -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 id 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/exons	MANE	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.1119C>T	p.Val373=	synonymous_variant	8/9	ENST00000300055.10
PLIN1	NM_001145311.2 linkuse as main transcript	c.1119C>T	p.Val373=	synonymous_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLIN1	ENST00000300055.10 linkuse as main transcript	c.1119C>T	p.Val373=	synonymous_variant	8/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2 linkuse as main transcript	c.1119C>T	p.Val373=	synonymous_variant	8/9	5		P1
PLIN1	ENST00000560330.1 linkuse as main transcript	c.123+72C>T		intron_variant		5

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

GnomAD3 exomes

AF:

0.284

AC:

71261

AN:

250828

Hom.:

10768

AF XY:

0.295

AC XY:

40048

AN XY:

135620

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 SAS exome

AF:

0.404

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

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.261

AC:

39695

AN:

152146

Hom.:

5605

Cov.:

AF XY:

0.256

AC XY:

19076

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.267

Hom.:

2875

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

DANN

Benign

0.50

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

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