dbSNP rs202141842: PLIN1:c.771+6T>C (chr15-89669494-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_002666.5(PLIN1):c.771+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,609,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

PLIN1
NM_002666.5 splice_region, intron

Scores

Splicing: ADA: 0.04484

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Publications

0 publications found

Variant links:

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

PLIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000501 (730/1457788) while in subpopulation NFE AF = 0.000526 (585/1111474). AF 95% confidence interval is 0.00049. There are 0 homozygotes in GnomAdExome4. There are 338 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.771+6T>C		splice_region_variant, intron_variant	Intron 6 of 8	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.771+6T>C		splice_region_variant, intron_variant	Intron 6 of 8		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN1	ENST00000300055.10 link	c.771+6T>C		splice_region_variant, intron_variant	Intron 6 of 8	1	NM_002666.5	ENSP00000300055.5		O60240
PLIN1	ENST00000430628.2 link	c.771+6T>C		splice_region_variant, intron_variant	Intron 6 of 8	5		ENSP00000402167.2		O60240

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000447

AC:

111

AN:

248378

AF XY:

0.000416

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000470

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000501

AC:

730

AN:

1457788

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

338

AN XY:

725340

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33440

American (AMR)

AF:

0.000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00352

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51032

Middle Eastern (MID)

AF:

0.000206

AC:

AN:

4854

European-Non Finnish (NFE)

AF:

0.000526

AC:

585

AN:

1111474

Other (OTH)

AF:

0.000647

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000302

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

67986

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000740

Hom.:

Bravo

AF:

0.000283

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 17, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.6

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.045

dbscSNV1_RF

Benign

0.18

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over