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GeneBe

rs1135628

chr11-823809-C-Achr11-823809-C-Gchr11-823809-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_020376.4(PNPLA2):c.873C>A(p.Pro291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,601,560 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 (★). Synonymous variant affecting the same amino acid position (i.e. P291P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

PNPLA2
NM_020376.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.58
Variant links:
Genes affected
PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-823809-C-A is Benign according to our data. Variant chr11-823809-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 465801.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.58 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000138 (21/152070) while in subpopulation NFE AF= 0.00028 (19/67936). AF 95% confidence interval is 0.000182. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNPLA2NM_020376.4 linkuse as main transcriptc.873C>A p.Pro291= synonymous_variant 7/10 ENST00000336615.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNPLA2ENST00000336615.9 linkuse as main transcriptc.873C>A p.Pro291= synonymous_variant 7/101 NM_020376.4 P1Q96AD5-1
ENST00000532946.1 linkuse as main transcriptn.361G>T non_coding_transcript_exon_variant 3/35

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000138
AC:
21
AN:
151952
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000280
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000103
AC:
23
AN:
222352
Hom.:
0
AF XY:
0.0000823
AC XY:
10
AN XY:
121488
show subpopulations
Gnomad AFR exome
AF:
0.0000751
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000540
Gnomad NFE exome
AF:
0.000164
Gnomad OTH exome
AF:
0.000180
GnomAD4 exome
AF:
0.0000993
AC:
144
AN:
1449490
Hom.:
0
Cov.:
57
AF XY:
0.0000986
AC XY:
71
AN XY:
720034
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000161
Gnomad4 ASJ exome
AF:
0.0000387
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000199
Gnomad4 NFE exome
AF:
0.000116
Gnomad4 OTH exome
AF:
0.000117
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000138
AC:
21
AN:
152070
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.000280
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000429
Hom.:
638

ClinVar

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

Submissions by phenotype

Neutral lipid storage myopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 04, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
0.062
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1135628; hg19: chr11-823809; API