15-89673865-C-T

Variant names:

• chr15-89673865-C-T
• rs2289487
• NM_002666.5:c.46-451G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002666.5(PLIN1):​c.46-451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,084 control chromosomes in the GnomAD database, including 23,143 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 0.54 (23143 hom., cov: 33)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48
• Publications: 43 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

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.46-451G>A		intron	N/A	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.46-451G>A		intron	N/A	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.46-451G>A		intron	N/A	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.46-451G>A		intron	N/A	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.46-451G>A		intron	N/A	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81840 AN: 151966 Hom.: 23139 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81879 AN: 152084 Hom.: 23143 Cov.: 33 AF XY: 0.536 AC XY: 39857 AN XY: 74360

African (AFR) AF: 0.372 AC: 15418 AN: 41470

American (AMR) AF: 0.501 AC: 7652 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1795 AN: 5166

South Asian (SAS) AF: 0.482 AC: 2322 AN: 4820

European-Finnish (FIN) AF: 0.628 AC: 6644 AN: 10578

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43956 AN: 67982

Other (OTH) AF: 0.555 AC: 1171 AN: 2110

Alfa AF: 0.603 Hom.: 86296

Bravo AF: 0.519

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0050
DANN	Benign	0.87
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289487; hg19: chr15-90217096;