rs3743373

chr15-89667688-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_002666.5(PLIN1):c.877G>A(p.Glu293Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,599,214 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00080 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (23 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027230382).
• BP6: Variant 15-89667688-C-T is Benign according to our data. Variant chr15-89667688-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000801 (122/152366) while in subpopulation EAS AF= 0.0122 (63/5168). AF 95% confidence interval is 0.00978. There are 1 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.877G>A	p.Glu293Lys	missense_variant	7/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.877G>A	p.Glu293Lys	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.877G>A	p.Glu293Lys	missense_variant	7/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.877G>A	p.Glu293Lys	missense_variant	7/9	5		P1
PLIN1	ENST00000560330.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.00806

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00213 AC: 462 AN: 217344 Hom.: 5 AF XY: 0.00259 AC XY: 304 AN XY: 117450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00989

Gnomad SAS exome AF: 0.00999

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.00119 AC: 1722 AN: 1446848 Hom.: 23 Cov.: 34 AF XY: 0.00144 AC XY: 1034 AN XY: 718452

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000239

Gnomad4 ASJ exome AF: 0.0000778

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.00910

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000177

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.000801 AC: 122 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.000819 AC XY: 61 AN XY: 74496

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.00827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000318 Hom.: 0

Bravo AF: 0.000593

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.00196 AC: 238

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.85	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.25	N;N
REVEL	Benign	0.065
Sift	Benign	0.059	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.023	B;B
Vest4		0.24
MVP		0.014
MPC		0.036
ClinPred		0.022	T
GERP RS		3.9
Varity_R		0.090
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3743373; hg19: chr15-90210919;