rs4520

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. G34G) has been classified as Uncertain significance.

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:7

Conservation

PhyloP100: -0.399

Publications

73 publications found

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 Gene-Disease associations (from GenCC):

cholesterol-ester transfer protein deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

APOC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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	A3KPE2

Ensembl Transcripts

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	P02656
APOC3	ENST00000630701.1	TSL:1	c.156T>C	p.Gly52Gly	synonymous	Exon 2 of 3	ENSP00000486182.1	B0YIW2
APOC3	ENST00000863804.1		c.159T>C	p.Gly53Gly	synonymous	Exon 3 of 4	ENSP00000533863.1

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

GnomAD2 exomes

AF:

0.647

AC:

161404

AN:

249582

AF XY:

0.649

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19115

38230

57345

76460

95575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20126

40252

60378

80504

100630

<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:

0.698

AC:

105895

AN:

151818

Hom.:

37554

Cov.:

AF XY:

0.687

AC XY:

50943

AN XY:

74152

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.722

Hom.:

69840

Bravo

AF:

0.698

Asia WGS

AF:

0.483

AC:

1683

AN:

3476

EpiCase

AF:

0.732

EpiControl

AF:

0.732

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Apolipoprotein c-III deficiency (1)

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.3

(source)

DANN

Benign

0.61

PhyloP100

-0.40

PromoterAI

0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over