chr11-116827022-C-A

Variant names:

• chr11-116827022-C-A
• rs2542051
• ENST00000863784.1:c.-196C>A

Variant summary

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

The ENST00000863784.1(APOC3):​c.-196C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,142 control chromosomes in the GnomAD database, including 22,499 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 0.53 (22499 hom., cov: 33)
• Consequence: APOC3 ENST00000863784.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 9 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

ENSG00000305923 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000863784.1. 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	ENST00000863784.1		c.-196C>A		5_prime_UTR	Exon 1 of 4	ENSP00000533843.1
	ENSG00000305923	ENST00000814126.1		n.136-1143C>A		intron	N/A
	APOC3	ENST00000863785.1		c.-132C>A		upstream_gene	N/A	ENSP00000533844.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80076 AN: 152024 Hom.: 22501 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.526 AC: 80096 AN: 152142 Hom.: 22499 Cov.: 33 AF XY: 0.521 AC XY: 38788 AN XY: 74384

African (AFR) AF: 0.315 AC: 13077 AN: 41490

American (AMR) AF: 0.566 AC: 8655 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3170 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2356 AN: 4828

European-Finnish (FIN) AF: 0.587 AC: 6220 AN: 10600

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42769 AN: 67972

Other (OTH) AF: 0.548 AC: 1158 AN: 2112

Alfa AF: 0.589 Hom.: 41011

Bravo AF: 0.525

Asia WGS AF: 0.536 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.022
DANN	Benign	0.78
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs2542051; hg19: chr11-116697738;