rs734104

chr11-116830144-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-116830144-C-T is Benign according to our data. Variant chr11-116830144-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
APOC3	NM_000040.3	c.-14+204C>T		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-14+204C>T		intron_variant		1	NM_000040.3	P1
APOC3	ENST00000375345.3	c.-37+204C>T		intron_variant		5
APOC3	ENST00000433777.5	c.-14+258C>T		intron_variant		5
APOC3	ENST00000470144.1	n.19+204C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.817

Alfa AF: 0.851 Hom.: 11160

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
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

Other links and lift over

dbSNP: rs734104; hg19: chr11-116700860;