rs2289487

Positions:

• chr15-89673865-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002666.5(PLIN1):​c.46-451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,084 control chromosomes in the GnomAD database, including 23,143 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 0.54 (23143 hom., cov: 33)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

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 (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5	c.46-451G>A		intron_variant		ENST00000300055.10
PLIN1	NM_001145311.2	c.46-451G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN1	ENST00000300055.10	c.46-451G>A		intron_variant		1	NM_002666.5	P1
PLIN1	ENST00000430628.2	c.46-451G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81840 AN: 151966 Hom.: 23139 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81879 AN: 152084 Hom.: 23143 Cov.: 33 AF XY: 0.536 AC XY: 39857 AN XY: 74360

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.555

Alfa AF: 0.621 Hom.: 59025

Bravo AF: 0.519

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0050
DANN	Benign	0.87

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: rs2289487; hg19: chr15-90217096;