15-89665079-A-T

Variant names:

• chr15-89665079-A-T
• rs1052700
• NM_002666.5:c.*504T>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.*504T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 375,166 control chromosomes in the GnomAD database, including 19,191 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 0.26 (6287 hom., cov: 31)
  • Exomes 𝑓: 0.33 (12904 hom.)
• Consequence: PLIN1 NM_002666.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 64 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 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.*504T>A		3_prime_UTR	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.*504T>A		3_prime_UTR	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.*504T>A		3_prime_UTR	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.*504T>A		3_prime_UTR	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.*504T>A		3_prime_UTR	Exon 9 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39799 AN: 151834 Hom.: 6291 Cov.: 31

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.332 AC: 74137 AN: 223214 Hom.: 12904 Cov.: 0 AF XY: 0.337 AC XY: 41944 AN XY: 124646

African (AFR) AF: 0.0773 AC: 472 AN: 6106

American (AMR) AF: 0.281 AC: 4272 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1989 AN: 5468

East Asian (EAS) AF: 0.418 AC: 3577 AN: 8562

South Asian (SAS) AF: 0.357 AC: 16113 AN: 45118

European-Finnish (FIN) AF: 0.284 AC: 2646 AN: 9320

Middle Eastern (MID) AF: 0.399 AC: 719 AN: 1802

European-Non Finnish (NFE) AF: 0.337 AC: 40778 AN: 120886

Other (OTH) AF: 0.332 AC: 3571 AN: 10746

GnomAD4 genome AF: 0.262 AC: 39784 AN: 151952 Hom.: 6287 Cov.: 31 AF XY: 0.262 AC XY: 19427 AN XY: 74250

African (AFR) AF: 0.0851 AC: 3530 AN: 41496

American (AMR) AF: 0.272 AC: 4153 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1250 AN: 3464

East Asian (EAS) AF: 0.411 AC: 2116 AN: 5146

South Asian (SAS) AF: 0.360 AC: 1736 AN: 4816

European-Finnish (FIN) AF: 0.287 AC: 3025 AN: 10544

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22944 AN: 67926

Other (OTH) AF: 0.300 AC: 631 AN: 2104

Alfa AF: 0.299 Hom.: 988

Bravo AF: 0.251

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		0.19
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: rs1052700; hg19: chr15-90208310; COSMIC: COSV55584367;