Variant rs3743373 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002666.5(PLIN1):c.877G>A(p.Glu293Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,599,214 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00080 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 23 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.414

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027230382).

BP6

Variant 15-89667688-C-T is Benign according to our data. Variant chr15-89667688-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000801 (122/152366) while in subpopulation EAS AF= 0.0122 (63/5168). AF 95% confidence interval is 0.00978. There are 1 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.877G>A	p.Glu293Lys	missense_variant	7/9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 linkuse as main transcript	c.877G>A	p.Glu293Lys	missense_variant	7/9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 linkuse as main transcript	c.877G>A	p.Glu293Lys	missense_variant	7/9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 linkuse as main transcript	c.877G>A	p.Glu293Lys	missense_variant	7/9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 linkuse as main transcript	c.-48G>A		upstream_gene_variant		5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0122

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00213

AC:

462

AN:

217344

Hom.:

AF XY:

0.00259

AC XY:

304

AN XY:

117450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00989

Gnomad SAS exome

AF:

0.00999

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.00144

GnomAD4 exome

AF:

0.00119

AC:

1722

AN:

1446848

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1034

AN XY:

718452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000239

Gnomad4 ASJ exome

AF:

0.0000778

Gnomad4 EAS exome

AF:

0.0155

Gnomad4 SAS exome

AF:

0.00910

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152366

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.00827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000593

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00196

AC:

238

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.73

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.35

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.065

Sift

Benign

0.059

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.023

B;B

Vest4

0.24

MVP

0.014

MPC

0.036

ClinPred

0.022

GERP RS

3.9

Varity_R

0.090

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over