rs58361219

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

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	O60240
PLIN1	NM_001145311.2 link	c.812C>T	p.Ala271Val	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.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.812C>T	p.Ala271Val	missense_variant	Exon 7 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.-113C>T		upstream_gene_variant		5		ENSP00000453426.1	H0YM16

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

GnomAD3 exomes

AF:

0.00155

AC:

262

AN:

169310

Hom.:

AF XY:

0.00128

AC XY:

115

AN XY:

89574

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 SAS exome

AF:

0.000295

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

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.000578

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000598

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.00575

AC:

876

AN:

152318

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00225

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

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

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

Varity_R

0.030

gMVP

0.18

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

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