rs4991027

chr19-4509047-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367868.2(PLIN4):c.3515-92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,268,130 control chromosomes in the GnomAD database, including 9,097 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 0.095 (875 hom., cov: 29)
  • Exomes 𝑓: 0.12 (8222 hom.)
• Consequence: PLIN4 NM_001367868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN4	NM_001367868.2	c.3515-92G>A		intron_variant		ENST00000301286.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN4	ENST00000301286.5	c.3515-92G>A		intron_variant		5	NM_001367868.2	P1
PLIN4	ENST00000633942.1	c.3518-92G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14494 AN: 151924 Hom.: 874 Cov.: 29

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.117 AC: 130172 AN: 1116088 Hom.: 8222 AF XY: 0.120 AC XY: 65839 AN XY: 550616

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.0791

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0999

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.0953 AC: 14493 AN: 152042 Hom.: 875 Cov.: 29 AF XY: 0.0967 AC XY: 7186 AN XY: 74336

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.0871

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.116

Alfa AF: 0.105 Hom.: 112

Bravo AF: 0.0908

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.066
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs4991027; hg19: chr19-4509059; COSMIC: COSV56698237;