Variant 19-4511718-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367868.2(PLIN4):c.2242A>G(p.Ile748Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,235,216 control chromosomes in the GnomAD database, including 413,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 14130 hom., cov: 10)

Exomes 𝑓: 0.83 ( 413760 hom. )

Failed GnomAD Quality Control

Consequence

PLIN4
NM_001367868.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0300

Variant links:

Genes affected

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

PLIN4 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=2.4908575E-6).

BP6

Variant 19-4511718-T-C is Benign according to our data. Variant chr19-4511718-T-C is described in ClinVar as [Benign]. Clinvar id is 403327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN4	NM_001367868.2 linkuse as main transcript	c.2242A>G	p.Ile748Val	missense_variant	5/8	ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN4	ENST00000301286.5 linkuse as main transcript	c.2242A>G	p.Ile748Val	missense_variant	5/8	5	NM_001367868.2	ENSP00000301286.4		Q96Q06
PLIN4	ENST00000633942.1 linkuse as main transcript	c.2245A>G	p.Ile749Val	missense_variant	5/8	5		ENSP00000488481.1		A0A0J9YXN7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

49213

AN:

70438

Hom.:

14121

Cov.:

FAILED QC

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.701

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.708

GnomAD3 exomes

AF:

0.791

AC:

176139

AN:

222694

Hom.:

65133

AF XY:

0.799

AC XY:

97706

AN XY:

122284

show subpopulations

Gnomad AFR exome

AF:

0.630

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.818

Gnomad EAS exome

AF:

0.811

Gnomad SAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.802

Gnomad NFE exome

AF:

0.797

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.833

AC:

1028831

AN:

1235216

Hom.:

413760

Cov.:

AF XY:

0.833

AC XY:

510095

AN XY:

612552

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.840

Gnomad4 ASJ exome

AF:

0.831

Gnomad4 EAS exome

AF:

0.909

Gnomad4 SAS exome

AF:

0.846

Gnomad4 FIN exome

AF:

0.858

Gnomad4 NFE exome

AF:

0.834

Gnomad4 OTH exome

AF:

0.824

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.699

AC:

49249

AN:

70494

Hom.:

14130

Cov.:

AF XY:

0.698

AC XY:

23703

AN XY:

33964

show subpopulations

Gnomad4 AFR

AF:

0.609

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.813

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.784

Hom.:

353

ExAC

AF:

0.841

AC:

98716

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.14

DANN

Benign

0.15

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.028

T;T

MetaRNN

Benign

0.0000025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.14

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.12

ClinPred

0.0052

GERP RS

4.6

Varity_R

0.030

gMVP

0.0074

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

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