rs1454633489

Variant names:

• chr15-89665713-G-A
• rs1454633489
• NM_002666.5:c.1439C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89665713-G-A
• chr15-89665713-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002666.5(PLIN1):​c.1439C>T​(p.Pro480Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,463,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.311
• Publications: 0 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: DEFINITIVE, STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03843996).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.1439C>T	p.Pro480Leu	missense	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1439C>T	p.Pro480Leu	missense	Exon 9 of 9	NP_001138783.1	O60240

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.1439C>T	p.Pro480Leu	missense	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1547C>T	p.Pro516Leu	missense	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1469C>T	p.Pro490Leu	missense	Exon 9 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 83116 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000305 AC: 4 AN: 1312594 Hom.: 0 Cov.: 31 AF XY: 0.00000309 AC XY: 2 AN XY: 646862

African (AFR) AF: 0.00 AC: 0 AN: 26814

American (AMR) AF: 0.00 AC: 0 AN: 27940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23212

East Asian (EAS) AF: 0.00 AC: 0 AN: 28958

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1042790

Other (OTH) AF: 0.0000185 AC: 1 AN: 54132

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73844

African (AFR) AF: 0.0000242 AC: 1 AN: 41268

American (AMR) AF: 0.00 AC: 0 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67834

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.31
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.0030	B
Vest4		0.042
MutPred		0.092		Loss of relative solvent accessibility (P = 0.0306)
MVP		0.014
MPC		1.2
ClinPred		0.039	T
GERP RS		0.28
Varity_R		0.049
gMVP		0.13
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1454633489; hg19: chr15-90208944;