19-4511943-T-C

Variant names:

• chr19-4511943-T-C
• rs7260518
• NM_001367868.2:c.2017A>G

Variant summary

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

The NM_001367868.2(PLIN4):​c.2017A>G​(p.Ser673Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 143,486 control chromosomes in the GnomAD database, including 57,388 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (57388 hom., cov: 27)
  • Exomes 𝑓: 0.88 (527512 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLIN4 NM_001367868.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 27 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 (MetaRNN=3.539672E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN4	NM_001367868.2	c.2017A>G	p.Ser673Gly	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.2017A>G	p.Ser673Gly	missense_variant	Exon 5 of 8	5	NM_001367868.2	ENSP00000301286.4
PLIN4	ENST00000633942.1	c.2020A>G	p.Ser674Gly	missense_variant	Exon 5 of 8	5		ENSP00000488481.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 128696 AN: 143362 Hom.: 57333 Cov.: 27

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.836

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.879

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.881 AC: 1197645 AN: 1359692 Hom.: 527512 Cov.: 104 AF XY: 0.877 AC XY: 590126 AN XY: 672678

African (AFR) AF: 0.926 AC: 29827 AN: 32208

American (AMR) AF: 0.931 AC: 37778 AN: 40566

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 21004 AN: 23118

East Asian (EAS) AF: 0.935 AC: 27765 AN: 29698

South Asian (SAS) AF: 0.781 AC: 56701 AN: 72630

European-Finnish (FIN) AF: 0.900 AC: 42219 AN: 46904

Middle Eastern (MID) AF: 0.841 AC: 4474 AN: 5318

European-Non Finnish (NFE) AF: 0.882 AC: 929785 AN: 1054622

Other (OTH) AF: 0.880 AC: 48092 AN: 54628

GnomAD4 genome AF: 0.898 AC: 128812 AN: 143486 Hom.: 57388 Cov.: 27 AF XY: 0.897 AC XY: 62762 AN XY: 69974

African (AFR) AF: 0.923 AC: 35901 AN: 38878

American (AMR) AF: 0.905 AC: 13138 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3067 AN: 3370

East Asian (EAS) AF: 0.931 AC: 4249 AN: 4564

South Asian (SAS) AF: 0.790 AC: 3386 AN: 4284

European-Finnish (FIN) AF: 0.903 AC: 8988 AN: 9948

Middle Eastern (MID) AF: 0.842 AC: 219 AN: 260

European-Non Finnish (NFE) AF: 0.884 AC: 57302 AN: 64814

Other (OTH) AF: 0.881 AC: 1730 AN: 1964

Alfa AF: 0.881 Hom.: 93567

ESP6500AA AF: 0.913 AC: 3735

ESP6500EA AF: 0.877 AC: 7343

ExAC AF: 0.805 AC: 97302

Asia WGS AF: 0.845 AC: 2820 AN: 3336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.13
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.10	T;T
MetaRNN	Benign	0.0000035	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;.
PhyloP100		-0.15
PrimateAI	Benign	0.24	T
PROVEAN	Benign	2.1	N;.
REVEL	Benign	0.14
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.14
ClinPred		0.042	T
GERP RS		3.7
Varity_R		0.038
gMVP		0.014
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: rs7260518; hg19: chr19-4511955; COSMIC: COSV107375137;