Genetic Variant PLIN4:c.3515-92G>A (chr19-4509047-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001367868.2(PLIN4):c.3515-92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,268,130 control chromosomes in the GnomAD database, including 9,097 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.095 ( 875 hom., cov: 29)

Exomes 𝑓: 0.12 ( 8222 hom. )

Consequence

PLIN4
NM_001367868.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

vacuolar Neuromyopathy
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

PLIN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLIN4	NM_001367868.2	MANE Select	c.3515-92G>A	intron	N/A	NP_001354797.1	Q96Q06
PLIN4	NM_001393888.1		c.3518-92G>A	intron	N/A	NP_001380817.1	A0A0J9YXN7
PLIN4	NM_001393889.1		c.3518-92G>A	intron	N/A	NP_001380818.1	A0A0J9YXN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.3515-92G>A	intron	N/A	ENSP00000301286.4	Q96Q06
PLIN4	ENST00000966625.1		c.3701-92G>A	intron	N/A	ENSP00000636684.1
PLIN4	ENST00000966622.1		c.3698-92G>A	intron	N/A	ENSP00000636681.1

Frequencies

GnomAD3 genomes

AF:

0.0954

AC:

14494

AN:

151924

Hom.:

874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0873

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0788

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.117

AC:

130172

AN:

1116088

Hom.:

8222

AF XY:

0.120

AC XY:

65839

AN XY:

550616

show subpopulations

African (AFR)

AF:

0.0353

AC:

882

AN:

25004

American (AMR)

AF:

0.0791

AC:

1831

AN:

23150

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

2886

AN:

18358

East Asian (EAS)

AF:

0.0999

AC:

3432

AN:

34362

South Asian (SAS)

AF:

0.191

AC:

11698

AN:

61362

European-Finnish (FIN)

AF:

0.102

AC:

3227

AN:

31566

Middle Eastern (MID)

AF:

0.169

AC:

782

AN:

4622

European-Non Finnish (NFE)

AF:

0.114

AC:

99528

AN:

869700

Other (OTH)

AF:

0.123

AC:

5906

AN:

47964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

5339

10677

16016

21354

26693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3512

7024

10536

14048

17560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0953

AC:

14493

AN:

152042

Hom.:

875

Cov.:

AF XY:

0.0967

AC XY:

7186

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0392

AC:

1628

AN:

41522

American (AMR)

AF:

0.0871

AC:

1330

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

564

AN:

3468

East Asian (EAS)

AF:

0.0788

AC:

406

AN:

5152

South Asian (SAS)

AF:

0.198

AC:

952

AN:

4814

European-Finnish (FIN)

AF:

0.107

AC:

1131

AN:

10570

Middle Eastern (MID)

AF:

0.192

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.119

AC:

8066

AN:

67934

Other (OTH)

AF:

0.116

AC:

245

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

595

1190

1785

2380

2975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.103

Hom.:

113

Bravo

AF:

0.0908

Asia WGS

AF:

0.142

AC:

494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.066

(source)

DANN

Benign

0.81

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over