Genetic Variant NM_001013706.3:c.721-129C>T (chr19-4525205-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013706.3(PLIN5):c.721-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 606,712 control chromosomes in the GnomAD database, including 1,206 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 0.050 ( 268 hom., cov: 31)

Exomes 𝑓: 0.058 ( 938 hom. )

Consequence

PLIN5
NM_001013706.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

2 publications found

Variant links:

Genes affected

PLIN5 (HGNC:33196): (perilipin 5) Predicted to enable identical protein binding activity and lipase binding activity. Predicted to be involved in several processes, including negative regulation of peroxisome proliferator activated receptor signaling pathway; regulation of lipase activity; and regulation of lipid metabolic process. Located in intracellular membrane-bounded organelle and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

PLIN5 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN5	NM_001013706.3 link	c.721-129C>T		intron_variant	Intron 6 of 7	ENST00000381848.7	NP_001013728.2	Q00G26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN5	ENST00000381848.7 link	c.721-129C>T		intron_variant	Intron 6 of 7	1	NM_001013706.3	ENSP00000371272.2		Q00G26
PLIN5	ENST00000589728.1 link	n.218-129C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0502

AC:

7643

AN:

152148

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0532

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0489

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0731

Gnomad OTH

AF:

0.0594

GnomAD4 exome

AF:

0.0582

AC:

26469

AN:

454446

Hom.:

938

AF XY:

0.0579

AC XY:

13572

AN XY:

234576

show subpopulations

African (AFR)

AF:

0.0112

AC:

124

AN:

11070

American (AMR)

AF:

0.0461

AC:

570

AN:

12358

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

1372

AN:

12356

East Asian (EAS)

AF:

0.000186

AC:

AN:

26922

South Asian (SAS)

AF:

0.0391

AC:

1337

AN:

34154

European-Finnish (FIN)

AF:

0.0451

AC:

1793

AN:

39736

Middle Eastern (MID)

AF:

0.0749

AC:

142

AN:

1896

European-Non Finnish (NFE)

AF:

0.0674

AC:

19621

AN:

291044

Other (OTH)

AF:

0.0604

AC:

1505

AN:

24910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1161

2321

3482

4642

5803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.0502

AC:

7639

AN:

152266

Hom.:

268

Cov.:

AF XY:

0.0486

AC XY:

3615

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0134

AC:

556

AN:

41552

American (AMR)

AF:

0.0531

AC:

813

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

416

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4822

European-Finnish (FIN)

AF:

0.0489

AC:

519

AN:

10610

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0731

AC:

4971

AN:

68008

Other (OTH)

AF:

0.0588

AC:

124

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

358

717

1075

1434

1792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0591

Hom.:

Bravo

AF:

0.0495

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.17

(source)

DANN

Benign

0.41

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over