11-116830819-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000040.3(APOC3):c.102T>C(p.Gly34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,612,544 control chromosomes in the GnomAD database, including 413,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37554 hom., cov: 30)

Exomes 𝑓: 0.71 ( 376007 hom. )

Consequence

APOC3
NM_000040.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.399

Variant links:

Genes affected

APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

APOC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 11-116830819-T-C is Benign according to our data. Variant chr11-116830819-T-C is described in ClinVar as [Benign]. Clinvar id is 518235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116830819-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.399 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3 linkuse as main transcript	c.102T>C	p.Gly34=	synonymous_variant	3/4	ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8 linkuse as main transcript	c.102T>C	p.Gly34=	synonymous_variant	3/4	1	NM_000040.3	P1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105868

AN:

151700

Hom.:

37553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.647

AC:

161404

AN:

249582

Hom.:

53853

AF XY:

0.649

AC XY:

87864

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.735

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.712

AC:

1040299

AN:

1460726

Hom.:

376007

Cov.:

AF XY:

0.707

AC XY:

513965

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.731

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.636

Gnomad4 NFE exome

AF:

0.747

Gnomad4 OTH exome

AF:

0.697

GnomAD4 genome

AF:

0.698

AC:

105895

AN:

151818

Hom.:

37554

Cov.:

AF XY:

0.687

AC XY:

50943

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.734

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.411

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.739

Gnomad4 OTH

AF:

0.678

Alfa

AF:

0.728

Hom.:

17442

Bravo

AF:

0.698

Asia WGS

AF:

0.483

AC:

1683

AN:

3476

EpiCase

AF:

0.732

EpiControl

AF:

0.732

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apolipoprotein c-III deficiency

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2018

This alteration is classified as 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

-0.96

Cadd

Benign

2.3

Dann

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over