Variant chr11-116830437-T-G 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.-13-133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 896,490 control chromosomes in the GnomAD database, including 120,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15938 hom., cov: 32)

Exomes 𝑓: 0.52 ( 104315 hom. )

Consequence

APOC3
NM_000040.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.367

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:

APOC3 (HGNC:):

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=-0.85).

BP6

Variant 11-116830437-T-G is Benign according to our data. Variant chr11-116830437-T-G is described in ClinVar as [Benign]. Clinvar id is 1283949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116830437-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 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.-13-133T>G		intron_variant		ENST00000227667.8	NP_000031.1	P02656A3KPE2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
APOC3	ENST00000227667.8 linkuse as main transcript	c.-13-133T>G	intron_variant	1	NM_000040.3	ENSP00000227667.2	P02656
APOC3	ENST00000375345.3 linkuse as main transcript	c.-36-56T>G	intron_variant	5		ENSP00000364494.1	B0YIW2
APOC3	ENST00000433777.5 linkuse as main transcript	c.-13-133T>G	intron_variant	5		ENSP00000410614.1	C9J2Q0
APOC3	ENST00000470144.1 linkuse as main transcript	n.20-133T>G	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65316

AN:

151902

Hom.:

15938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.521

AC:

387983

AN:

744470

Hom.:

104315

AF XY:

0.515

AC XY:

198889

AN XY:

386120

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.566

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.548

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.493

GnomAD4 genome

AF:

0.430

AC:

65337

AN:

152020

Hom.:

15938

Cov.:

AF XY:

0.427

AC XY:

31750

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.543

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.475

Hom.:

2289

Bravo

AF:

0.422

Asia WGS

AF:

0.356

AC:

1241

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.4

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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