chr15-89668913-T-C

Variant names:

• chr15-89668913-T-C
• rs8179043
• NM_002666.5:c.771+587A>G

Variant summary

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

The NM_002666.5(PLIN1):​c.771+587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,144 control chromosomes in the GnomAD database, including 27,296 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 0.58 (27296 hom., cov: 32)
• Consequence: PLIN1 NM_002666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 20 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: STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5	c.771+587A>G		intron_variant	Intron 6 of 8	ENST00000300055.10	NP_002657.3
PLIN1	NM_001145311.2	c.771+587A>G		intron_variant	Intron 6 of 8		NP_001138783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10	c.771+587A>G		intron_variant	Intron 6 of 8	1	NM_002666.5	ENSP00000300055.5
PLIN1	ENST00000430628.2	c.771+587A>G		intron_variant	Intron 6 of 8	5		ENSP00000402167.2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88550 AN: 152026 Hom.: 27292 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.582 AC: 88590 AN: 152144 Hom.: 27296 Cov.: 32 AF XY: 0.580 AC XY: 43110 AN XY: 74376

African (AFR) AF: 0.389 AC: 16145 AN: 41496

American (AMR) AF: 0.546 AC: 8351 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1845 AN: 5178

South Asian (SAS) AF: 0.574 AC: 2769 AN: 4824

European-Finnish (FIN) AF: 0.663 AC: 7020 AN: 10582

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48083 AN: 67996

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.659 Hom.: 63616

Bravo AF: 0.560

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.82
PhyloP100		0.24
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: rs8179043; hg19: chr15-90212144;