rs140081686

chr15-89673353-C-Achr15-89673353-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002666.5(PLIN1):c.107G>T(p.Cys36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 1,602,546 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (8 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.67

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008116901).
• BP6: Variant 15-89673353-C-A is Benign according to our data. Variant chr15-89673353-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 393441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000592 (90/152004) while in subpopulation NFE AF= 0.000221 (15/67928). AF 95% confidence interval is 0.000135. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.107G>T	p.Cys36Phe	missense_variant	3/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.107G>T	p.Cys36Phe	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.107G>T	p.Cys36Phe	missense_variant	3/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.107G>T	p.Cys36Phe	missense_variant	3/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.000593 AC: 90 AN: 151886 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00116 AC: 265 AN: 228968 Hom.: 0 AF XY: 0.00106 AC XY: 131 AN XY: 123362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.0000525

Gnomad NFE exome AF: 0.000341

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000585 AC: 848 AN: 1450542 Hom.: 8 Cov.: 32 AF XY: 0.000591 AC XY: 426 AN XY: 720274

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000202

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome AF: 0.000592 AC: 90 AN: 152004 Hom.: 0 Cov.: 33 AF XY: 0.000578 AC XY: 43 AN XY: 74340

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00130 Hom.: 5

Bravo AF: 0.000548

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000825 AC: 100

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Monogenic diabetes Benign:1

Likely benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Apr 08, 2016

ACMG Criteria: PP3, BS2 (type2diabetesgenetics.org), BP4 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0081	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.59	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.11
Sift	Benign	0.097	T;T
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.47
MVP		0.49
MPC		0.19
ClinPred		0.066	T
GERP RS		4.9
Varity_R		0.31
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140081686; hg19: chr15-90216584;