rs618354

chr11-116830061-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000040.3(APOC3):c.-14+121G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 185,628 control chromosomes in the GnomAD database, including 7,787 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 0.28 (6884 hom., cov: 32)
  • Exomes 𝑓: 0.21 (903 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.-14+121G>C		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-14+121G>C		intron_variant		1	NM_000040.3	P1
APOC3	ENST00000375345.3	c.-37+121G>C		intron_variant		5
APOC3	ENST00000433777.5	c.-14+175G>C		intron_variant		5
APOC3	ENST00000470144.1	n.19+121G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42591 AN: 151790 Hom.: 6886 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.207 AC: 6975 AN: 33720 Hom.: 903 AF XY: 0.205 AC XY: 3546 AN XY: 17286

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.0497

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.280 AC: 42610 AN: 151908 Hom.: 6884 Cov.: 32 AF XY: 0.274 AC XY: 20319 AN XY: 74286

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0603

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.262

Alfa AF: 0.270 Hom.: 721

Bravo AF: 0.290

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.3
Dann	Benign	0.44

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: rs618354; hg19: chr11-116700777;