19-4506903-A-G

Variant names:

• chr19-4506903-A-G
• rs11673616
• NM_001367868.2:c.3702+1865T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367868.2(PLIN4):​c.3702+1865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,304 control chromosomes in the GnomAD database, including 894 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 0.097 (894 hom., cov: 33)
• Consequence: PLIN4 NM_001367868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	NM_001367868.2	MANE Select	c.3702+1865T>C		intron	N/A	NP_001354797.1	Q96Q06
	PLIN4	NM_001393888.1		c.3705+1865T>C		intron	N/A	NP_001380817.1	A0A0J9YXN7
	PLIN4	NM_001393889.1		c.3705+1865T>C		intron	N/A	NP_001380818.1	A0A0J9YXN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN4	ENST00000301286.5	TSL:5 MANE Select	c.3702+1865T>C		intron	N/A	ENSP00000301286.4	Q96Q06
	PLIN4	ENST00000966625.1		c.3888+1865T>C		intron	N/A	ENSP00000636684.1
	PLIN4	ENST00000966622.1		c.3885+1865T>C		intron	N/A	ENSP00000636681.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14729 AN: 152186 Hom.: 893 Cov.: 33

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.0967 AC: 14729 AN: 152304 Hom.: 894 Cov.: 33 AF XY: 0.0981 AC XY: 7303 AN XY: 74472

African (AFR) AF: 0.0416 AC: 1729 AN: 41586

American (AMR) AF: 0.0889 AC: 1360 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3470

East Asian (EAS) AF: 0.0805 AC: 417 AN: 5182

South Asian (SAS) AF: 0.199 AC: 961 AN: 4828

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10614

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8125 AN: 68000

Other (OTH) AF: 0.121 AC: 255 AN: 2114

Alfa AF: 0.110 Hom.: 1098

Bravo AF: 0.0921

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.53
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs11673616; hg19: chr19-4506915;