rs140081686

Variant names:

• chr15-89673353-C-A
• rs140081686
• NM_002666.5:c.107G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89673353-C-A
• chr15-89673353-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002666.5(PLIN1):​c.107G>T​(p.Cys36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 1,602,546 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 0.00059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (8 hom.)
• Consequence: PLIN1 NM_002666.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.67
• Publications: 7 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008116901).
• BP6: Variant 15-89673353-C-A is Benign according to our data. Variant chr15-89673353-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 393441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 90 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.107G>T	p.Cys36Phe	missense	Exon 3 of 9	NP_002657.3
	PLIN1	NM_001145311.2		c.107G>T	p.Cys36Phe	missense	Exon 3 of 9	NP_001138783.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.107G>T	p.Cys36Phe	missense	Exon 3 of 9	ENSP00000300055.5
	PLIN1	ENST00000896664.1		c.107G>T	p.Cys36Phe	missense	Exon 3 of 9	ENSP00000566723.1
	PLIN1	ENST00000896666.1		c.107G>T	p.Cys36Phe	missense	Exon 3 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes AF: 0.000593 AC: 90 AN: 151886 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00116 AC: 265 AN: 228968 AF XY: 0.00106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000525

Gnomad NFE exome AF: 0.000341

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000585 AC: 848 AN: 1450542 Hom.: 8 Cov.: 32 AF XY: 0.000591 AC XY: 426 AN XY: 720274

African (AFR) AF: 0.000150 AC: 5 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 43310

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 576 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.000202 AC: 17 AN: 84036

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52550

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1106448

Other (OTH) AF: 0.00175 AC: 105 AN: 59950

GnomAD4 genome AF: 0.000592 AC: 90 AN: 152004 Hom.: 0 Cov.: 33 AF XY: 0.000578 AC XY: 43 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67928

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00117 Hom.: 5

Bravo AF: 0.000548

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000825 AC: 100

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Monogenic diabetes (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.097	T
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.49
MPC		0.19
ClinPred		0.066	T
GERP RS		4.9
Varity_R		0.31
gMVP		0.50
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140081686; hg19: chr15-90216584;