rs2304795

Variant names:

• chr15-89667032-A-G
• rs2304795
• NM_002666.5:c.1113T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-89667032-A-G
• chr15-89667032-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002666.5(PLIN1):​c.1113T>C​(p.Pro371Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,613,576 control chromosomes in the GnomAD database, including 116,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11091 hom., cov: 33)
  • Exomes 𝑓: 0.38 (105711 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.85
• Publications: 56 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 15-89667032-A-G is Benign according to our data. Variant chr15-89667032-A-G is described in ClinVar as Benign. ClinVar VariationId is 129970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 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.1113T>C	p.Pro371Pro	synonymous	Exon 8 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1113T>C	p.Pro371Pro	synonymous	Exon 8 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.1113T>C	p.Pro371Pro	synonymous	Exon 8 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1221T>C	p.Pro407Pro	synonymous	Exon 8 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1143T>C	p.Pro381Pro	synonymous	Exon 8 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57550 AN: 151992 Hom.: 11100 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.411

GnomAD2 exomes AF: 0.379 AC: 94980 AN: 250832 AF XY: 0.387

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.377 AC: 551566 AN: 1461466 Hom.: 105711 Cov.: 47 AF XY: 0.382 AC XY: 277840 AN XY: 727038

African (AFR) AF: 0.383 AC: 12818 AN: 33478

American (AMR) AF: 0.341 AC: 15238 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10406 AN: 26132

East Asian (EAS) AF: 0.276 AC: 10938 AN: 39694

South Asian (SAS) AF: 0.516 AC: 44497 AN: 86236

European-Finnish (FIN) AF: 0.340 AC: 18182 AN: 53404

Middle Eastern (MID) AF: 0.436 AC: 2503 AN: 5738

European-Non Finnish (NFE) AF: 0.372 AC: 413866 AN: 1111708

Other (OTH) AF: 0.383 AC: 23118 AN: 60390

GnomAD4 genome AF: 0.378 AC: 57562 AN: 152110 Hom.: 11091 Cov.: 33 AF XY: 0.377 AC XY: 28049 AN XY: 74366

African (AFR) AF: 0.387 AC: 16091 AN: 41532

American (AMR) AF: 0.362 AC: 5541 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1377 AN: 3464

East Asian (EAS) AF: 0.281 AC: 1444 AN: 5146

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4826

European-Finnish (FIN) AF: 0.344 AC: 3640 AN: 10594

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25588 AN: 67936

Other (OTH) AF: 0.405 AC: 856 AN: 2114

Alfa AF: 0.373 Hom.: 5398

Bravo AF: 0.375

Asia WGS AF: 0.408 AC: 1417 AN: 3478

EpiCase AF: 0.387

EpiControl AF: 0.390

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	PLIN1-related familial partial lipodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.025
DANN	Benign	0.36
PhyloP100		-3.9
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: rs2304795; hg19: chr15-90210263; COSMIC: COSV55583698;