11-116830819-T-C

Variant names:

• chr11-116830819-T-C
• rs4520
• NM_000040.3:c.102T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000040.3(APOC3):​c.102T>C​(p.Gly34Gly) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.399
• Publications: 73 publications found

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 Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 518235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	NM_000040.3	MANE Select	c.102T>C	p.Gly34Gly	synonymous	Exon 3 of 4	NP_000031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	ENST00000227667.8	TSL:1 MANE Select	c.102T>C	p.Gly34Gly	synonymous	Exon 3 of 4	ENSP00000227667.2
	APOC3	ENST00000630701.1	TSL:1	c.156T>C	p.Gly52Gly	synonymous	Exon 2 of 3	ENSP00000486182.1
	APOC3	ENST00000375345.3	TSL:5	c.156T>C	p.Gly52Gly	synonymous	Exon 3 of 4	ENSP00000364494.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105868 AN: 151700 Hom.: 37553 Cov.: 30

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

GnomAD2 exomes AF: 0.647 AC: 161404 AN: 249582 AF XY: 0.649

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 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.: 71 AF XY: 0.707 AC XY: 513965 AN XY: 726652

African (AFR) AF: 0.731 AC: 24481 AN: 33476

American (AMR) AF: 0.523 AC: 23360 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18345 AN: 26128

East Asian (EAS) AF: 0.401 AC: 15919 AN: 39682

South Asian (SAS) AF: 0.562 AC: 48461 AN: 86224

European-Finnish (FIN) AF: 0.636 AC: 33443 AN: 52578

Middle Eastern (MID) AF: 0.659 AC: 3793 AN: 5760

European-Non Finnish (NFE) AF: 0.747 AC: 830439 AN: 1111844

Other (OTH) AF: 0.697 AC: 42058 AN: 60374

GnomAD4 genome AF: 0.698 AC: 105895 AN: 151818 Hom.: 37554 Cov.: 30 AF XY: 0.687 AC XY: 50943 AN XY: 74152

African (AFR) AF: 0.734 AC: 30422 AN: 41424

American (AMR) AF: 0.599 AC: 9156 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2436 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2110 AN: 5128

South Asian (SAS) AF: 0.544 AC: 2596 AN: 4772

European-Finnish (FIN) AF: 0.626 AC: 6610 AN: 10562

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50182 AN: 67880

Other (OTH) AF: 0.678 AC: 1427 AN: 2106

Alfa AF: 0.722 Hom.: 69840

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Apolipoprotein c-III deficiency Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Cardiovascular phenotype Benign:1

Dec 11, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-0.40
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs4520; hg19: chr11-116701535; COSMIC: COSV52635206; COSMIC: COSV52635206;