Genetic Variant PLIN1:c.772-23T>A (chr15-89667816-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002666.5(PLIN1):c.772-23T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,546,456 control chromosomes in the GnomAD database, including 736,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68524 hom., cov: 34)

Exomes 𝑓: 0.98 ( 668163 hom. )

Consequence

PLIN1
NM_002666.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.01

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 (BayesDel_noAF=-0.93).

BP6

Variant 15-89667816-A-T is Benign according to our data. Variant chr15-89667816-A-T is described in ClinVar as [Benign]. Clinvar id is 1250333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.772-23T>A		intron_variant	Intron 6 of 8	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.772-23T>A		intron_variant	Intron 6 of 8		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 link	c.772-23T>A	intron_variant	Intron 6 of 8	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.772-23T>A	intron_variant	Intron 6 of 8	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.-176T>A	upstream_gene_variant		5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

144041

AN:

152190

Hom.:

68488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.942

Gnomad FIN

AF:

0.951

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.941

GnomAD3 exomes

AF:

0.923

AC:

139202

AN:

150790

Hom.:

65011

AF XY:

0.932

AC XY:

74418

AN XY:

79884

show subpopulations

Gnomad AFR exome

AF:

0.920

Gnomad AMR exome

AF:

0.775

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

0.732

Gnomad SAS exome

AF:

0.947

Gnomad FIN exome

AF:

0.952

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.944

GnomAD4 exome

AF:

0.977

AC:

1362369

AN:

1394148

Hom.:

668163

Cov.:

AF XY:

0.977

AC XY:

672255

AN XY:

687938

show subpopulations

Gnomad4 AFR exome

AF:

0.918

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

0.713

Gnomad4 SAS exome

AF:

0.951

Gnomad4 FIN exome

AF:

0.953

Gnomad4 NFE exome

AF:

0.997

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.946

AC:

144134

AN:

152308

Hom.:

68524

Cov.:

AF XY:

0.941

AC XY:

70081

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.942

Gnomad4 FIN

AF:

0.951

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.936

Alfa

AF:

0.977

Hom.:

13334

Bravo

AF:

0.933

Asia WGS

AF:

0.834

AC:

2901

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PLIN1-related familial partial lipodystrophy

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0030

DANN

Benign

0.76

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