NM_002666.5:c.1395C>A

Variant names:

• chr15-89665757-G-T
• rs747073444
• NM_002666.5:c.1395C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_002666.5(PLIN1):​c.1395C>A​(p.Pro465Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,273,980 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P465P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.07
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-89665757-G-T is Benign according to our data. Variant chr15-89665757-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3044124.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000199 (30/150880) while in subpopulation SAS AF = 0.00518 (25/4826). AF 95% confidence interval is 0.0036. There are 1 homozygotes in GnomAd4. There are 21 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 30 AD gene.

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.1395C>A	p.Pro465Pro	synonymous	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1395C>A	p.Pro465Pro	synonymous	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.1395C>A	p.Pro465Pro	synonymous	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1503C>A	p.Pro501Pro	synonymous	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1425C>A	p.Pro475Pro	synonymous	Exon 9 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.000199 AC: 30 AN: 150772 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000739

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00355 AC: 17 AN: 4788 AF XY: 0.00397

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000239 AC: 268 AN: 1123100 Hom.: 2 Cov.: 31 AF XY: 0.000314 AC XY: 170 AN XY: 540948

African (AFR) AF: 0.00 AC: 0 AN: 22624

American (AMR) AF: 0.00 AC: 0 AN: 8460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14292

East Asian (EAS) AF: 0.00 AC: 0 AN: 25754

South Asian (SAS) AF: 0.00624 AC: 201 AN: 32234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24026

Middle Eastern (MID) AF: 0.00134 AC: 4 AN: 2994

European-Non Finnish (NFE) AF: 0.0000475 AC: 45 AN: 947958

Other (OTH) AF: 0.000402 AC: 18 AN: 44758

GnomAD4 genome AF: 0.000199 AC: 30 AN: 150880 Hom.: 1 Cov.: 32 AF XY: 0.000285 AC XY: 21 AN XY: 73724

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000739 AC: 5 AN: 67680

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PLIN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs747073444; hg19: chr15-90208988; COSMIC: COSV105890516;