15-89665760-C-T

Variant names:

• chr15-89665760-C-T
• rs536062857
• NM_002666.5:c.1392G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_002666.5(PLIN1):​c.1392G>A​(p.Ala464Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,122,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A464A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS2: High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.1392G>A	p.Ala464Ala	synonymous_variant	Exon 9 of 9	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.1392G>A	p.Ala464Ala	synonymous_variant	Exon 9 of 9		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.1392G>A	p.Ala464Ala	synonymous_variant	Exon 9 of 9	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.1392G>A	p.Ala464Ala	synonymous_variant	Exon 9 of 9	5		ENSP00000402167.2
PLIN1	ENST00000560330.1	c.124-819G>A		intron_variant	Intron 2 of 2	5		ENSP00000453426.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000624 AC: 7 AN: 1122440 Hom.: 0 Cov.: 31 AF XY: 0.00000185 AC XY: 1 AN XY: 540572

Gnomad4 AFR exome AF: 0.0000442

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000633

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.3
DANN	Benign	0.93

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: rs536062857; hg19: chr15-90208991;