NM_001367868.2:c.2242A>G

Variant names:

• chr19-4511718-T-C
• rs62115190
• NM_001367868.2:c.2242A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367868.2(PLIN4):​c.2242A>G​(p.Ile748Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,235,216 control chromosomes in the GnomAD database, including 413,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (14130 hom., cov: 10)
  • Exomes 𝑓: 0.83 (413760 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.4908575E-6).
• BP6: Variant 19-4511718-T-C is Benign according to our data. Variant chr19-4511718-T-C is described in ClinVar as Benign. ClinVar VariationId is 403327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 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.2242A>G	p.Ile748Val	missense	Exon 5 of 8	NP_001354797.1	Q96Q06
	PLIN4	NM_001393888.1		c.2245A>G	p.Ile749Val	missense	Exon 5 of 8	NP_001380817.1	A0A0J9YXN7
	PLIN4	NM_001393889.1		c.2245A>G	p.Ile749Val	missense	Exon 5 of 8	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.2242A>G	p.Ile748Val	missense	Exon 5 of 8	ENSP00000301286.4	Q96Q06
	PLIN4	ENST00000966625.1		c.2428A>G	p.Ile810Val	missense	Exon 6 of 9	ENSP00000636684.1
	PLIN4	ENST00000966622.1		c.2425A>G	p.Ile809Val	missense	Exon 6 of 9	ENSP00000636681.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 49213 AN: 70438 Hom.: 14121 Cov.: 10

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.791 AC: 176139 AN: 222694 AF XY: 0.799

Gnomad AFR exome AF: 0.630

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.818

Gnomad EAS exome AF: 0.811

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.833 AC: 1028831 AN: 1235216 Hom.: 413760 Cov.: 70 AF XY: 0.833 AC XY: 510095 AN XY: 612552

African (AFR) AF: 0.636 AC: 17655 AN: 27738

American (AMR) AF: 0.840 AC: 29587 AN: 35226

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 17729 AN: 21342

East Asian (EAS) AF: 0.909 AC: 28306 AN: 31126

South Asian (SAS) AF: 0.846 AC: 57493 AN: 67990

European-Finnish (FIN) AF: 0.858 AC: 35630 AN: 41538

Middle Eastern (MID) AF: 0.847 AC: 4122 AN: 4864

European-Non Finnish (NFE) AF: 0.834 AC: 797429 AN: 955756

Other (OTH) AF: 0.824 AC: 40880 AN: 49636

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.699 AC: 49249 AN: 70494 Hom.: 14130 Cov.: 10 AF XY: 0.698 AC XY: 23703 AN XY: 33964

African (AFR) AF: 0.609 AC: 14326 AN: 23516

American (AMR) AF: 0.702 AC: 4252 AN: 6058

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 1234 AN: 1622

East Asian (EAS) AF: 0.813 AC: 1590 AN: 1956

South Asian (SAS) AF: 0.736 AC: 1380 AN: 1874

European-Finnish (FIN) AF: 0.766 AC: 3014 AN: 3934

Middle Eastern (MID) AF: 0.731 AC: 98 AN: 134

European-Non Finnish (NFE) AF: 0.744 AC: 22380 AN: 30070

Other (OTH) AF: 0.709 AC: 655 AN: 924

Alfa AF: 0.784 Hom.: 353

ExAC AF: 0.841 AC: 98716

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.14
DANN	Benign	0.15
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.028	T
MetaRNN	Benign	0.0000025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.030
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
ClinPred		0.0052	T
GERP RS		4.6
Varity_R		0.030
gMVP		0.0074
Mutation Taster		=99/1	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: rs62115190; hg19: chr19-4511730; COSMIC: COSV56686401;