NM_001367868.2:c.3515-92G>T

Variant names:

• chr19-4509047-C-A
• rs4991027
• NM_001367868.2:c.3515-92G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367868.2(PLIN4):​c.3515-92G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000895 in 1,117,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: PLIN4 NM_001367868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	NM_001367868.2	MANE Select	c.3515-92G>T		intron	N/A	NP_001354797.1
	PLIN4	NM_001393888.1		c.3518-92G>T		intron	N/A	NP_001380817.1
	PLIN4	NM_001393889.1		c.3518-92G>T		intron	N/A	NP_001380818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.3515-92G>T		intron	N/A	ENSP00000301286.4
	PLIN4	ENST00000633942.1	TSL:5	c.3518-92G>T		intron	N/A	ENSP00000488481.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.95e-7 AC: 1 AN: 1117414 Hom.: 0 AF XY: 0.00000181 AC XY: 1 AN XY: 551264

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25010

American (AMR) AF: 0.00 AC: 0 AN: 23166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18370

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34376

South Asian (SAS) AF: 0.00 AC: 0 AN: 61424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 870816

Other (OTH) AF: 0.00 AC: 0 AN: 48026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.036
DANN	Benign	0.66
PhyloP100		-2.3

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: rs4991027; hg19: chr19-4509059;