15-89665760-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 1 publications found

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]

PLIN1 Gene-Disease associations (from GenCC):

• PLIN1-related familial partial lipodystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.1392G>A	p.Ala464Ala	synonymous	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1392G>A	p.Ala464Ala	synonymous	Exon 9 of 9	NP_001138783.1	O60240

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.1392G>A	p.Ala464Ala	synonymous	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1500G>A	p.Ala500Ala	synonymous	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1422G>A	p.Ala474Ala	synonymous	Exon 9 of 9	ENSP00000566725.1

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

African (AFR) AF: 0.0000442 AC: 1 AN: 22618

American (AMR) AF: 0.00 AC: 0 AN: 8452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14282

East Asian (EAS) AF: 0.00 AC: 0 AN: 25730

South Asian (SAS) AF: 0.00 AC: 0 AN: 32068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2994

European-Non Finnish (NFE) AF: 0.00000633 AC: 6 AN: 947606

Other (OTH) AF: 0.00 AC: 0 AN: 44688

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.3
DANN	Benign	0.93
PhyloP100		-0.68

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

Other links and lift over

dbSNP: rs536062857; hg19: chr15-90208991;