19-4514123-C-T

Variant names:

• chr19-4514123-C-T
• rs4807598
• NM_001367868.2:c.259-422G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_001367868.2(PLIN4):​c.259-422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,292 control chromosomes in the GnomAD database, including 69,375 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 0.95 (69375 hom., cov: 33)
• Consequence: PLIN4 NM_001367868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 3 publications found

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]

PLIN4 Gene-Disease associations (from GenCC):

• vacuolar Neuromyopathy

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2	c.259-422G>A		intron_variant	Intron 4 of 7	ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN4	ENST00000301286.5	c.259-422G>A		intron_variant	Intron 4 of 7	5	NM_001367868.2	ENSP00000301286.4
PLIN4	ENST00000633942.1	c.259-419G>A		intron_variant	Intron 4 of 7	5		ENSP00000488481.1

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145213 AN: 152174 Hom.: 69324 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.954

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.954 AC: 145322 AN: 152292 Hom.: 69375 Cov.: 33 AF XY: 0.953 AC XY: 70983 AN XY: 74464

African (AFR) AF: 0.966 AC: 40148 AN: 41566

American (AMR) AF: 0.964 AC: 14744 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3305 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5066 AN: 5190

South Asian (SAS) AF: 0.901 AC: 4351 AN: 4828

European-Finnish (FIN) AF: 0.945 AC: 10032 AN: 10620

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64482 AN: 68006

Other (OTH) AF: 0.955 AC: 2019 AN: 2114

Alfa AF: 0.951 Hom.: 134897

Bravo AF: 0.959

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	19
DANN	Benign	0.37
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.56		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4807598; hg19: chr19-4514135;