NM_002666.5:c.772-799G>A

Variant names:

• chr15-89668592-C-T
• rs894160
• NM_002666.5:c.772-799G>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.772-799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,058 control chromosomes in the GnomAD database, including 6,589 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 0.29 (6589 hom., cov: 32)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 73 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.772-799G>A		intron_variant	Intron 6 of 8	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.772-799G>A		intron_variant	Intron 6 of 8		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.772-799G>A		intron_variant	Intron 6 of 8	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.772-799G>A		intron_variant	Intron 6 of 8	5		ENSP00000402167.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44629 AN: 151940 Hom.: 6583 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.294 AC: 44657 AN: 152058 Hom.: 6589 Cov.: 32 AF XY: 0.294 AC XY: 21834 AN XY: 74324

African (AFR) AF: 0.292 AC: 12126 AN: 41474

American (AMR) AF: 0.276 AC: 4210 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1983 AN: 5168

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4812

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10564

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19665 AN: 67980

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.292 Hom.: 9766

Bravo AF: 0.294

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs894160; hg19: chr15-90211823; COSMIC: COSV55584003; COSMIC: COSV55584003;