11-116830953-G-C

Position:

• chr11-116830953-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000040.3(APOC3):​c.179+57G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,181,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0013 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAd4 at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC3	NM_000040.3	c.179+57G>C		intron_variant		ENST00000227667.8	NP_000031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC3	ENST00000227667.8	c.179+57G>C		intron_variant		1	NM_000040.3	ENSP00000227667.2
APOC3	ENST00000630701.1	c.233+57G>C		intron_variant		1		ENSP00000486182.1
APOC3	ENST00000375345.3	c.233+57G>C		intron_variant		5		ENSP00000364494.1
APOC3	ENST00000470144.1	n.211+57G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 144 AN: 111410 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000505

Gnomad ASJ AF: 0.000391

Gnomad EAS AF: 0.000540

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000512

Gnomad OTH AF: 0.00273

GnomAD4 exome AF: 0.00000934 AC: 10 AN: 1070166 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 6 AN XY: 539004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000326

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.0000287

Gnomad4 NFE exome AF: 0.00000887

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00129 AC: 144 AN: 111514 Hom.: 0 Cov.: 23 AF XY: 0.00154 AC XY: 82 AN XY: 53194

Gnomad4 AFR AF: 0.00276

Gnomad4 AMR AF: 0.000504

Gnomad4 ASJ AF: 0.000391

Gnomad4 EAS AF: 0.000539

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000512

Gnomad4 OTH AF: 0.00271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.54

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: rs2070667; hg19: chr11-116701669;