19-4504876-G-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001367868.2(PLIN4):​c.3774C>T​(p.Asp1258Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,606,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PLIN4
NM_001367868.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

Publications

1 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 19-4504876-G-A is Benign according to our data. Variant chr19-4504876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3890518.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.16 with no splicing effect.
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLIN4NM_001367868.2 linkc.3774C>T p.Asp1258Asp synonymous_variant Exon 7 of 8 ENST00000301286.5 NP_001354797.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLIN4ENST00000301286.5 linkc.3774C>T p.Asp1258Asp synonymous_variant Exon 7 of 8 5 NM_001367868.2 ENSP00000301286.4 Q96Q06
PLIN4ENST00000633942.1 linkc.3777C>T p.Asp1259Asp synonymous_variant Exon 7 of 8 5 ENSP00000488481.1 A0A0J9YXN7

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000256
AC:
6
AN:
234630
AF XY:
0.0000392
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000187
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000254
AC:
37
AN:
1454472
Hom.:
0
Cov.:
31
AF XY:
0.0000304
AC XY:
22
AN XY:
722942
show subpopulations
African (AFR)
AF:
0.0000300
AC:
1
AN:
33384
American (AMR)
AF:
0.00
AC:
0
AN:
43822
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25876
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39518
South Asian (SAS)
AF:
0.000130
AC:
11
AN:
84874
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51716
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.0000207
AC:
23
AN:
1109370
Other (OTH)
AF:
0.0000332
AC:
2
AN:
60154
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41570
American (AMR)
AF:
0.000131
AC:
2
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5178
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68022
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 14, 2025
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.4
DANN
Benign
0.85
PhyloP100
-1.2

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

Publications

Other links and lift over

dbSNP: rs201822855; hg19: chr19-4504888; API