11-116829426-T-C

Variant names:

• chr11-116829426-T-C
• rs2854117
• ENST00000863789.1:c.-920T>C

Variant summary

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

The ENST00000863789.1(APOC3):​c.-920T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,110 control chromosomes in the GnomAD database, including 28,902 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 0.59 (28902 hom., cov: 33)
• Consequence: APOC3 ENST00000863789.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 201 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 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.-920T>C		5_prime_UTR	Exon 1 of 4	ENSP00000533848.1
	APOC3	ENST00000863790.1		c.-619T>C		5_prime_UTR	Exon 1 of 5	ENSP00000533849.1
	APOC3	ENST00000863791.1		c.-468T>C		5_prime_UTR	Exon 1 of 4	ENSP00000533850.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89736 AN: 151992 Hom.: 28900 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.590 AC: 89779 AN: 152110 Hom.: 28902 Cov.: 33 AF XY: 0.584 AC XY: 43395 AN XY: 74346

African (AFR) AF: 0.323 AC: 13413 AN: 41496

American (AMR) AF: 0.622 AC: 9510 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2454 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2899 AN: 5154

South Asian (SAS) AF: 0.556 AC: 2683 AN: 4822

European-Finnish (FIN) AF: 0.652 AC: 6903 AN: 10594

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49770 AN: 67960

Other (OTH) AF: 0.620 AC: 1309 AN: 2110

Alfa AF: 0.678 Hom.: 22912

Bravo AF: 0.584

Asia WGS AF: 0.535 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		0.94
PromoterAI		-0.027	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2854117; hg19: chr11-116700142;