chr11-116829453-C-T

Variant names:

• chr11-116829453-C-T
• rs2854116
• ENST00000863789.1:c.-893C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000863789.1(APOC3):​c.-893C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,934 control chromosomes in the GnomAD database, including 21,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21877 hom., cov: 33)
• Consequence: APOC3 ENST00000863789.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 191 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000863789.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	ENST00000863789.1		c.-893C>T		5_prime_UTR	Exon 1 of 4	ENSP00000533848.1
	APOC3	ENST00000863790.1		c.-592C>T		5_prime_UTR	Exon 1 of 5	ENSP00000533849.1
	APOC3	ENST00000863791.1		c.-441C>T		5_prime_UTR	Exon 1 of 4	ENSP00000533850.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78625 AN: 151818 Hom.: 21882 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78649 AN: 151934 Hom.: 21877 Cov.: 33 AF XY: 0.512 AC XY: 38039 AN XY: 74234

African (AFR) AF: 0.298 AC: 12337 AN: 41418

American (AMR) AF: 0.566 AC: 8651 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2918 AN: 5134

South Asian (SAS) AF: 0.481 AC: 2314 AN: 4812

European-Finnish (FIN) AF: 0.576 AC: 6101 AN: 10592

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42429 AN: 67908

Other (OTH) AF: 0.534 AC: 1124 AN: 2106

Alfa AF: 0.557 Hom.: 8715

Bravo AF: 0.516

Asia WGS AF: 0.487 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.46
PhyloP100		0.087
PromoterAI		-0.030	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2854116; hg19: chr11-116700169;