rs8179074

chr15-89665904-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002666.5(PLIN1):c.1248C>T(p.Phe416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,535,726 control chromosomes in the GnomAD database, including 2,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (180 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2018 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 15-89665904-G-A is Benign according to our data. Variant chr15-89665904-G-A is described in ClinVar as [Benign]. Clinvar id is 129972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89665904-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.1248C>T	p.Phe416=	synonymous_variant	9/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.1248C>T	p.Phe416=	synonymous_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.1248C>T	p.Phe416=	synonymous_variant	9/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.1248C>T	p.Phe416=	synonymous_variant	9/9	5		P1
PLIN1	ENST00000560330.1	c.124-963C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6077 AN: 152088 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.00958

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0473

GnomAD3 exomes AF: 0.0387 AC: 5975 AN: 154556 Hom.: 164 AF XY: 0.0394 AC XY: 3431 AN XY: 87124

Gnomad AFR exome AF: 0.00782

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0181

Gnomad FIN exome AF: 0.0495

Gnomad NFE exome AF: 0.0530

Gnomad OTH exome AF: 0.0574

GnomAD4 exome AF: 0.0506 AC: 70041 AN: 1383524 Hom.: 2018 Cov.: 31 AF XY: 0.0500 AC XY: 34281 AN XY: 685416

Gnomad4 AFR exome AF: 0.00807

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0628

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0566

Gnomad4 NFE exome AF: 0.0561

Gnomad4 OTH exome AF: 0.0481

GnomAD4 genome AF: 0.0399 AC: 6075 AN: 152202 Hom.: 180 Cov.: 32 AF XY: 0.0394 AC XY: 2932 AN XY: 74428

Gnomad4 AFR AF: 0.00955

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0558

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0493 Hom.: 48

Bravo AF: 0.0379

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 05, 2013

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Benign	0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs8179074; hg19: chr15-90209135; COSMIC: COSV55583479;