15-89665079-A-T

Position:

• chr15-89665079-A-T

Variant summary

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

The NM_002666.5(PLIN1):​c.*504T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 375,166 control chromosomes in the GnomAD database, including 19,191 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 0.26 (6287 hom., cov: 31)
  • Exomes 𝑓: 0.33 (12904 hom.)
• Consequence: PLIN1 NM_002666.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.*504T>A		3_prime_UTR_variant	9/9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.*504T>A		3_prime_UTR_variant	9/9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055	c.*504T>A		3_prime_UTR_variant	9/9	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628	c.*504T>A		3_prime_UTR_variant	9/9	5		ENSP00000402167.2
PLIN1	ENST00000560330.1	c.124-138T>A		intron_variant		5		ENSP00000453426.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39799 AN: 151834 Hom.: 6291 Cov.: 31

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.332 AC: 74137 AN: 223214 Hom.: 12904 Cov.: 0 AF XY: 0.337 AC XY: 41944 AN XY: 124646

Gnomad4 AFR exome AF: 0.0773

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.262 AC: 39784 AN: 151952 Hom.: 6287 Cov.: 31 AF XY: 0.262 AC XY: 19427 AN XY: 74250

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.300

Alfa AF: 0.299 Hom.: 988

Bravo AF: 0.251

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1052700; hg19: chr15-90208310; COSMIC: COSV55584367;