chr19-4525205-G-A

Variant names:

• chr19-4525205-G-A
• rs11670485
• NM_001013706.3:c.721-129C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 2 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN5	NM_001013706.3	MANE Select	c.721-129C>T		intron	N/A	NP_001013728.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN5	ENST00000381848.7	TSL:1 MANE Select	c.721-129C>T		intron	N/A	ENSP00000371272.2
	PLIN5	ENST00000905186.1		c.958-129C>T		intron	N/A	ENSP00000575245.1
	PLIN5	ENST00000905182.1		c.922-129C>T		intron	N/A	ENSP00000575241.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7643 AN: 152148 Hom.: 268 Cov.: 31

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

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: 5 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

GnomAD4 genome AF: 0.0502 AC: 7639 AN: 152266 Hom.: 268 Cov.: 31 AF XY: 0.0486 AC XY: 3615 AN XY: 74448

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: 2 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: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4971 AN: 68008

Other (OTH) AF: 0.0588 AC: 124 AN: 2108

Alfa AF: 0.0591 Hom.: 42

Bravo AF: 0.0495

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.41
PhyloP100		-3.6
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: rs11670485; hg19: chr19-4525217;