Variant 15-89665760-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002666.5(PLIN1):c.1392G>T(p.Ala464=) 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 Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 7 hom. )

Consequence

PLIN1
NM_002666.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.679

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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]. Clinvar id is 710652.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89665760-C-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.1392G>T	p.Ala464=	synonymous_variant	9/9	ENST00000300055.10
PLIN1	NM_001145311.2 linkuse as main transcript	c.1392G>T	p.Ala464=	synonymous_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLIN1	ENST00000300055.10 linkuse as main transcript	c.1392G>T	p.Ala464=	synonymous_variant	9/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2 linkuse as main transcript	c.1392G>T	p.Ala464=	synonymous_variant	9/9	5		P1
PLIN1	ENST00000560330.1 linkuse as main transcript	c.124-819G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

391

AN:

150732

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0117

AC:

AN:

4788

Hom.:

AF XY:

0.0110

AC XY:

AN XY:

3264

show subpopulations

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 SAS exome

AF:

0.00110

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.:

Cov.:

AF XY:

0.00345

AC XY:

1864

AN XY:

540570

show subpopulations

Gnomad4 AFR exome

AF:

0.000531

Gnomad4 AMR exome

AF:

0.000237

Gnomad4 ASJ exome

AF:

0.000140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00333

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00259

AC:

391

AN:

150840

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

206

AN XY:

73712

show subpopulations

Gnomad4 AFR

AF:

0.000411

Gnomad4 AMR

AF:

0.000330

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00383

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00173

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.5

DANN

Benign

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over