rs7250947

Positions:

• chr19-4510518-G-A

Variant summary

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

The NM_001367868.2(PLIN4):​c.3442C>T​(p.Arg1148Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,480,548 control chromosomes in the GnomAD database, including 5,534 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1148H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.091 (711 hom., cov: 33)
  • Exomes 𝑓: 0.081 (4823 hom.)
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (MetaRNN=0.002263546).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN4	NM_001367868.2	c.3442C>T	p.Arg1148Cys	missense_variant	5/8	ENST00000301286.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN4	ENST00000301286.5	c.3442C>T	p.Arg1148Cys	missense_variant	5/8	5	NM_001367868.2	P1
PLIN4	ENST00000633942.1	c.3445C>T	p.Arg1149Cys	missense_variant	5/8	5

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13798 AN: 152160 Hom.: 710 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0958

GnomAD3 exomes AF: 0.0685 AC: 11074 AN: 161756 Hom.: 485 AF XY: 0.0672 AC XY: 5794 AN XY: 86262

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0431

Gnomad NFE exome AF: 0.0870

Gnomad OTH exome AF: 0.0750

GnomAD4 exome AF: 0.0811 AC: 107726 AN: 1328270 Hom.: 4823 Cov.: 36 AF XY: 0.0795 AC XY: 51443 AN XY: 647408

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.0563

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.000162

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.0789

GnomAD4 genome AF: 0.0907 AC: 13806 AN: 152278 Hom.: 711 Cov.: 33 AF XY: 0.0863 AC XY: 6428 AN XY: 74456

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0881

Gnomad4 OTH AF: 0.0953

Alfa AF: 0.0867 Hom.: 1026

Bravo AF: 0.0973

TwinsUK AF: 0.0976 AC: 362

ALSPAC AF: 0.0861 AC: 332

ESP6500AA AF: 0.116 AC: 485

ESP6500EA AF: 0.0822 AC: 692

ExAC AF: 0.0652 AC: 7685

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.51	T;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.11
Sift	Benign	0.070	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.96	D;.
Vest4		0.14
ClinPred		0.048	T
GERP RS		-7.8
Varity_R		0.046
gMVP		0.13

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: rs7250947; hg19: chr19-4510530; COSMIC: COSV56689924;