rs5128

Variant summary

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

The ENST00000227667.8(APOC3):​c.*40G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,612,872 control chromosomes in the GnomAD database, including 630,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56779 hom., cov: 33)
Exomes 𝑓: 0.88 ( 573988 hom. )

Consequence

APOC3
ENST00000227667.8 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -2.16
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]

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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=-0.83).
BP6
Variant 11-116832924-G-C is Benign according to our data. Variant chr11-116832924-G-C is described in ClinVar as [Benign]. Clinvar id is 1250845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116832924-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APOC3NM_000040.3 linkuse as main transcriptc.*40G>C 3_prime_UTR_variant 4/4 ENST00000227667.8 NP_000031.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APOC3ENST00000227667.8 linkuse as main transcriptc.*40G>C 3_prime_UTR_variant 4/41 NM_000040.3 ENSP00000227667 P1
APOC3ENST00000630701.1 linkuse as main transcriptc.*40G>C 3_prime_UTR_variant 3/31 ENSP00000486182
APOC3ENST00000375345.3 linkuse as main transcriptc.*40G>C 3_prime_UTR_variant 4/45 ENSP00000364494

Frequencies

GnomAD3 genomes
AF:
0.862
AC:
131089
AN:
152120
Hom.:
56755
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.848
Gnomad AMI
AF:
0.947
Gnomad AMR
AF:
0.806
Gnomad ASJ
AF:
0.858
Gnomad EAS
AF:
0.686
Gnomad SAS
AF:
0.684
Gnomad FIN
AF:
0.867
Gnomad MID
AF:
0.848
Gnomad NFE
AF:
0.907
Gnomad OTH
AF:
0.858
GnomAD3 exomes
AF:
0.839
AC:
210515
AN:
250898
Hom.:
89243
AF XY:
0.836
AC XY:
113526
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.843
Gnomad AMR exome
AF:
0.787
Gnomad ASJ exome
AF:
0.860
Gnomad EAS exome
AF:
0.697
Gnomad SAS exome
AF:
0.697
Gnomad FIN exome
AF:
0.872
Gnomad NFE exome
AF:
0.906
Gnomad OTH exome
AF:
0.863
GnomAD4 exome
AF:
0.884
AC:
1290860
AN:
1460634
Hom.:
573988
Cov.:
48
AF XY:
0.878
AC XY:
638016
AN XY:
726638
show subpopulations
Gnomad4 AFR exome
AF:
0.843
Gnomad4 AMR exome
AF:
0.791
Gnomad4 ASJ exome
AF:
0.861
Gnomad4 EAS exome
AF:
0.671
Gnomad4 SAS exome
AF:
0.698
Gnomad4 FIN exome
AF:
0.873
Gnomad4 NFE exome
AF:
0.913
Gnomad4 OTH exome
AF:
0.870
GnomAD4 genome
AF:
0.862
AC:
131167
AN:
152238
Hom.:
56779
Cov.:
33
AF XY:
0.854
AC XY:
63577
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.848
Gnomad4 AMR
AF:
0.805
Gnomad4 ASJ
AF:
0.858
Gnomad4 EAS
AF:
0.686
Gnomad4 SAS
AF:
0.683
Gnomad4 FIN
AF:
0.867
Gnomad4 NFE
AF:
0.907
Gnomad4 OTH
AF:
0.853
Alfa
AF:
0.882
Hom.:
10905
Bravo
AF:
0.863
Asia WGS
AF:
0.687
AC:
2394
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 30, 2018This variant is associated with the following publications: (PMID: 27624799, 15100713, 19034316) -
Myocardial infarction, susceptibility to Uncertain:1
Uncertain significance, no assertion criteria providedreference populationiDNA Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.98
DANN
Benign
0.72
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.

Other links and lift over

dbSNP: rs5128; hg19: chr11-116703640; COSMIC: COSV52636718; COSMIC: COSV52636718; API