rs734104

Variant names:

• chr11-116830144-C-T
• rs734104
• NM_000040.3:c.-14+204C>T

Variant summary

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

The NM_000040.3(APOC3):​c.-14+204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,980 control chromosomes in the GnomAD database, including 51,329 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 0.82 (51329 hom., cov: 30)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.13
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC3	NM_000040.3	c.-14+204C>T		intron_variant	Intron 1 of 3	ENST00000227667.8	NP_000031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC3	ENST00000227667.8	c.-14+204C>T		intron_variant	Intron 1 of 3	1	NM_000040.3	ENSP00000227667.2
APOC3	ENST00000375345.3	c.-37+204C>T		intron_variant	Intron 1 of 3	5		ENSP00000364494.1
APOC3	ENST00000433777.5	c.-14+258C>T		intron_variant	Intron 1 of 2	5		ENSP00000410614.1
APOC3	ENST00000470144.1	n.19+204C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124511 AN: 151862 Hom.: 51324 Cov.: 30

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.820 AC: 124568 AN: 151980 Hom.: 51329 Cov.: 30 AF XY: 0.810 AC XY: 60141 AN XY: 74262

African (AFR) AF: 0.801 AC: 33184 AN: 41448

American (AMR) AF: 0.760 AC: 11618 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2855 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3498 AN: 5146

South Asian (SAS) AF: 0.671 AC: 3231 AN: 4812

European-Finnish (FIN) AF: 0.776 AC: 8193 AN: 10560

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59135 AN: 67944

Other (OTH) AF: 0.817 AC: 1727 AN: 2114

Alfa AF: 0.850 Hom.: 83738

Bravo AF: 0.825

Asia WGS AF: 0.671 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.44
PhyloP100		-4.1
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs734104; hg19: chr11-116700860;