Variant rs4225 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000040.3(APOC3):c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,606,286 control chromosomes in the GnomAD database, including 274,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18615 hom., cov: 33)

Exomes 𝑓: 0.58 ( 256337 hom. )

Consequence

APOC3
NM_000040.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.142

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-116832955-G-T is Benign according to our data. Variant chr11-116832955-G-T is described in ClinVar as [Benign]. Clinvar id is 1225805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116832955-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC3	NM_000040.3 linkuse as main transcript	c.*71G>T		3_prime_UTR_variant	4/4	ENST00000227667.8	NP_000031.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
APOC3	ENST00000227667.8 linkuse as main transcript	c.*71G>T	3_prime_UTR_variant	4/4	1	NM_000040.3	ENSP00000227667	P1
APOC3	ENST00000630701.1 linkuse as main transcript	c.*71G>T	3_prime_UTR_variant	3/3	1		ENSP00000486182
APOC3	ENST00000375345.3 linkuse as main transcript	c.*71G>T	3_prime_UTR_variant	4/4	5		ENSP00000364494

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68199

AN:

151968

Hom.:

18618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.579

AC:

841593

AN:

1454200

Hom.:

256337

Cov.:

AF XY:

0.572

AC XY:

414102

AN XY:

723704

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.638

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.448

AC:

68184

AN:

152086

Hom.:

18615

Cov.:

AF XY:

0.440

AC XY:

32704

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.540

Gnomad4 NFE

AF:

0.627

Gnomad4 OTH

AF:

0.471

Alfa

AF:

0.479

Hom.:

2945

Bravo

AF:

0.433

Asia WGS

AF:

0.215

AC:

752

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 30420299, 30782561, 27624799) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.2

DANN

Benign

0.76

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.

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