rs8179070

Positions:

• chr15-89667745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002666.5(PLIN1):​c.820C>T​(p.Arg274Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,566,348 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012048215).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000223 (34/152314) while in subpopulation SAS AF= 0.00207 (10/4826). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.820C>T	p.Arg274Trp	missense_variant	7/9	ENST00000300055.10
PLIN1	NM_001145311.2	c.820C>T	p.Arg274Trp	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.820C>T	p.Arg274Trp	missense_variant	7/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.820C>T	p.Arg274Trp	missense_variant	7/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000448 AC: 77 AN: 172024 Hom.: 0 AF XY: 0.000494 AC XY: 45 AN XY: 91152

Gnomad AFR exome AF: 0.0000944

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000377

Gnomad SAS exome AF: 0.00117

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 227 AN: 1414034 Hom.: 1 Cov.: 34 AF XY: 0.000193 AC XY: 135 AN XY: 698698

Gnomad4 AFR exome AF: 0.000153

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000400

Gnomad4 SAS exome AF: 0.000857

Gnomad4 FIN exome AF: 0.0000402

Gnomad4 NFE exome AF: 0.0000809

Gnomad4 OTH exome AF: 0.000136

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22 AN XY: 74460

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.000246

ExAC AF: 0.000376 AC: 44

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.012	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.48
MVP		0.20
MPC		0.18
ClinPred		0.079	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.94
Varity_R		0.088
gMVP		0.35

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: rs8179070; hg19: chr15-90210976;