rs2304796

Variant names:

• chr15-89667026-G-A
• rs2304796
• NM_002666.5:c.1119C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89667026-G-A
• chr15-89667026-G-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.1119C>T​(p.Val373Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,584 control chromosomes in the GnomAD database, including 74,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5605 hom., cov: 33)
  • Exomes 𝑓: 0.30 (69181 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.15
• Publications: 19 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=-0.81).
• BP6: Variant 15-89667026-G-A is Benign according to our data. Variant chr15-89667026-G-A is described in ClinVar as Benign. ClinVar VariationId is 129971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) 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.1119C>T	p.Val373Val	synonymous	Exon 8 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1119C>T	p.Val373Val	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.1119C>T	p.Val373Val	synonymous	Exon 8 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1227C>T	p.Val409Val	synonymous	Exon 8 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1149C>T	p.Val383Val	synonymous	Exon 8 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39684 AN: 152028 Hom.: 5604 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.277

GnomAD2 exomes AF: 0.284 AC: 71261 AN: 250828 AF XY: 0.295

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.290

GnomAD4 exome AF: 0.304 AC: 444295 AN: 1461438 Hom.: 69181 Cov.: 40 AF XY: 0.309 AC XY: 224320 AN XY: 727024

African (AFR) AF: 0.163 AC: 5450 AN: 33472

American (AMR) AF: 0.187 AC: 8358 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9454 AN: 26130

East Asian (EAS) AF: 0.279 AC: 11082 AN: 39692

South Asian (SAS) AF: 0.403 AC: 34760 AN: 86232

European-Finnish (FIN) AF: 0.211 AC: 11254 AN: 53406

Middle Eastern (MID) AF: 0.324 AC: 1859 AN: 5736

European-Non Finnish (NFE) AF: 0.309 AC: 343614 AN: 1111684

Other (OTH) AF: 0.306 AC: 18464 AN: 60390

GnomAD4 genome AF: 0.261 AC: 39695 AN: 152146 Hom.: 5605 Cov.: 33 AF XY: 0.256 AC XY: 19076 AN XY: 74378

African (AFR) AF: 0.175 AC: 7252 AN: 41532

American (AMR) AF: 0.230 AC: 3523 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1554 AN: 5146

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4830

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10604

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21096 AN: 67950

Other (OTH) AF: 0.274 AC: 579 AN: 2110

Alfa AF: 0.254 Hom.: 3063

Bravo AF: 0.255

Asia WGS AF: 0.326 AC: 1133 AN: 3478

EpiCase AF: 0.312

EpiControl AF: 0.316

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	-0.81
CADD	Benign	6.8
DANN	Benign	0.50
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs2304796; hg19: chr15-90210257; COSMIC: COSV55583571;