rs145476436

chr15-89667751-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.814G>A(p.Val272Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,564,906 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00083 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (10 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.59

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=0.008209467).
• BP6: Variant 15-89667751-C-T is Benign according to our data. Variant chr15-89667751-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 393437.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 = 0.000828 (126/152238) while in subpopulation NFE AF= 0.000176 (12/68050). AF 95% confidence interval is 0.000102. There are 3 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.814G>A	p.Val272Met	missense_variant	7/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.814G>A	p.Val272Met	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.814G>A	p.Val272Met	missense_variant	7/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.814G>A	p.Val272Met	missense_variant	7/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152238 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00177 AC: 303 AN: 170880 Hom.: 0 AF XY: 0.00168 AC XY: 152 AN XY: 90514

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000354

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000524

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.000680 AC: 960 AN: 1412668 Hom.: 10 Cov.: 35 AF XY: 0.000692 AC XY: 483 AN XY: 697878

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00211

GnomAD4 genome AF: 0.000828 AC: 126 AN: 152238 Hom.: 3 Cov.: 33 AF XY: 0.000672 AC XY: 50 AN XY: 74362

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000955

Alfa AF: 0.00176 Hom.: 0

Bravo AF: 0.000971

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00152 AC: 13

ExAC AF: 0.000877 AC: 102

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

Jun 23, 2015

ACMG Criteria: BS2, BP4 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.0082	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	0.50	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.095	T;T
Polyphen		0.99	D;D
Vest4		0.37
MVP		0.19
MPC		0.17
ClinPred		0.063	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.94
Varity_R		0.13
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs145476436; hg19: chr15-90210982;