chr19-4510518-G-A

Variant names:

• chr19-4510518-G-A
• rs7250947
• NM_001367868.2:c.3442C>T

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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 rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2	c.3442C>T	p.Arg1148Cys	missense_variant	Exon 5 of 8	ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN4	ENST00000301286.5	c.3442C>T	p.Arg1148Cys	missense_variant	Exon 5 of 8	5	NM_001367868.2	ENSP00000301286.4
PLIN4	ENST00000633942.1	c.3445C>T	p.Arg1149Cys	missense_variant	Exon 5 of 8	5		ENSP00000488481.1

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;.
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;