NM_002666.5:c.-15+528G>C

Variant names:

• chr15-89678723-C-G
• rs4578621
• NM_002666.5:c.-15+528G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002666.5(PLIN1):​c.-15+528G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,056 control chromosomes in the GnomAD database, including 53,112 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 0.82 (53112 hom., cov: 30)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 10 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]

PEX11A (HGNC:8852): (peroxisomal biogenesis factor 11 alpha) This gene is a member of the PEX11 family, which is composed of membrane elongation factors involved in regulation of peroxisome maintenance and proliferation. This gene product interacts with peroxisomal membrane protein 19 and may respond to outside stimuli to increase peroxisome abundance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

PEX11A Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

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.-15+528G>C		intron	N/A	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.-15+599G>C		intron	N/A	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.-15+528G>C		intron	N/A	ENSP00000300055.5	O60240
	PLIN1	ENST00000531697.1	TSL:1	n.96+599G>C		intron	N/A
	PLIN1	ENST00000896669.1		c.-81G>C		5_prime_UTR	Exon 2 of 10	ENSP00000566728.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125364 AN: 151938 Hom.: 53087 Cov.: 30

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.825 AC: 125434 AN: 152056 Hom.: 53112 Cov.: 30 AF XY: 0.816 AC XY: 60659 AN XY: 74322

African (AFR) AF: 0.767 AC: 31792 AN: 41468

American (AMR) AF: 0.711 AC: 10861 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3277 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1637 AN: 5146

South Asian (SAS) AF: 0.702 AC: 3368 AN: 4796

European-Finnish (FIN) AF: 0.854 AC: 9034 AN: 10576

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62575 AN: 68002

Other (OTH) AF: 0.834 AC: 1759 AN: 2110

Alfa AF: 0.849 Hom.: 2804

Bravo AF: 0.810

Asia WGS AF: 0.509 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.84
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs4578621; hg19: chr15-90221954;