15-89665760-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002666.5(PLIN1):​c.1392G>T​(p.Ala464Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,273,274 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (7 hom.)
• Consequence: PLIN1 NM_002666.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 15-89665760-C-A is Benign according to our data. Variant chr15-89665760-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 710652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.679 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00259 (391/150840) while in subpopulation NFE AF = 0.00337 (228/67662). AF 95% confidence interval is 0.00301. There are 1 homozygotes in GnomAd4. There are 206 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 391 AD gene.

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>T	p.Ala464Ala	synonymous	Exon 9 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.1392G>T	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>T	p.Ala464Ala	synonymous	Exon 9 of 9	ENSP00000300055.5	O60240
	PLIN1	ENST00000896664.1		c.1500G>T	p.Ala500Ala	synonymous	Exon 9 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.1422G>T	p.Ala474Ala	synonymous	Exon 9 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 391 AN: 150732 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.0177

Gnomad AMR AF: 0.000331

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.00387

GnomAD2 exomes AF: 0.0117 AC: 56 AN: 4788 AF XY: 0.0110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0472

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.00335 AC: 3756 AN: 1122434 Hom.: 7 Cov.: 31 AF XY: 0.00345 AC XY: 1864 AN XY: 540570

African (AFR) AF: 0.000531 AC: 12 AN: 22618

American (AMR) AF: 0.000237 AC: 2 AN: 8452

Ashkenazi Jewish (ASJ) AF: 0.000140 AC: 2 AN: 14282

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

South Asian (SAS) AF: 0.00131 AC: 42 AN: 32068

European-Finnish (FIN) AF: 0.0190 AC: 457 AN: 24000

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

European-Non Finnish (NFE) AF: 0.00333 AC: 3155 AN: 947602

Other (OTH) AF: 0.00192 AC: 86 AN: 44688

GnomAD4 genome AF: 0.00259 AC: 391 AN: 150840 Hom.: 1 Cov.: 32 AF XY: 0.00279 AC XY: 206 AN XY: 73712

African (AFR) AF: 0.000411 AC: 17 AN: 41380

American (AMR) AF: 0.000330 AC: 5 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000391 AC: 2 AN: 5110

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0111 AC: 111 AN: 9960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00337 AC: 228 AN: 67662

Other (OTH) AF: 0.00383 AC: 8 AN: 2090

Alfa AF: 0.00202 Hom.: 0

Bravo AF: 0.00173

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PLIN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.5
DANN	Benign	0.80
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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;