15-89673215-G-A

Variant names:

• chr15-89673215-G-A
• rs150004289
• NM_002666.5:c.245C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002666.5(PLIN1):​c.245C>T​(p.Thr82Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00228 in 1,563,422 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (5 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.73
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• PLIN1-related familial partial lipodystrophy

  Inheritance: AD Classification: STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02043277).
• BP6: Variant 15-89673215-G-A is Benign according to our data. Variant chr15-89673215-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 393440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00153 (233/152256) while in subpopulation NFE AF = 0.00253 (172/68016). AF 95% confidence interval is 0.00222. There are 2 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 233 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.245C>T	p.Thr82Ile	missense	Exon 3 of 9	NP_002657.3
	PLIN1	NM_001145311.2		c.245C>T	p.Thr82Ile	missense	Exon 3 of 9	NP_001138783.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.245C>T	p.Thr82Ile	missense	Exon 3 of 9	ENSP00000300055.5
	PLIN1	ENST00000430628.2	TSL:5	c.245C>T	p.Thr82Ile	missense	Exon 3 of 9	ENSP00000402167.2

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152138 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00138 AC: 243 AN: 175882 AF XY: 0.00155

Gnomad AFR exome AF: 0.000291

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00136

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000129

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00236 AC: 3330 AN: 1411166 Hom.: 5 Cov.: 32 AF XY: 0.00226 AC XY: 1576 AN XY: 697590

African (AFR) AF: 0.000311 AC: 10 AN: 32144

American (AMR) AF: 0.00117 AC: 45 AN: 38620

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 49 AN: 25302

East Asian (EAS) AF: 0.0000272 AC: 1 AN: 36806

South Asian (SAS) AF: 0.000174 AC: 14 AN: 80406

European-Finnish (FIN) AF: 0.000264 AC: 13 AN: 49244

Middle Eastern (MID) AF: 0.000622 AC: 3 AN: 4826

European-Non Finnish (NFE) AF: 0.00283 AC: 3071 AN: 1085480

Other (OTH) AF: 0.00213 AC: 124 AN: 58338

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152256 Hom.: 2 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74438

African (AFR) AF: 0.000698 AC: 29 AN: 41554

American (AMR) AF: 0.00105 AC: 16 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00253 AC: 172 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00221 Hom.: 2

Bravo AF: 0.00153

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000683 AC: 3

ESP6500EA AF: 0.00292 AC: 25

ExAC AF: 0.000639 AC: 76

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Monogenic diabetes Benign:1

May 17, 2016

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria: PP3, BS1 (ExAC), BS2 (ExAC), BP4

not provided Benign:1

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLIN1: BP4, BS1

PLIN1-related disorder Benign:1

Jul 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.47
MVP		0.26
MPC		0.20
ClinPred		0.043	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.64
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150004289; hg19: chr15-90216446;