11-116830437-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000040.3(APOC3):c.-13-133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 896,490 control chromosomes in the GnomAD database, including 120,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (15938 hom., cov: 32)
  • Exomes 𝑓: 0.52 (104315 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-116830437-T-G is Benign according to our data. Variant chr11-116830437-T-G is described in ClinVar as [Benign]. Clinvar id is 1283949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116830437-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.-13-133T>G		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-13-133T>G		intron_variant		1	NM_000040.3	P1
APOC3	ENST00000375345.3	c.-36-56T>G		intron_variant		5
APOC3	ENST00000433777.5	c.-13-133T>G		intron_variant		5
APOC3	ENST00000470144.1	n.20-133T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65316 AN: 151902 Hom.: 15938 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.521 AC: 387983 AN: 744470 Hom.: 104315 AF XY: 0.515 AC XY: 198889 AN XY: 386120

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.430 AC: 65337 AN: 152020 Hom.: 15938 Cov.: 32 AF XY: 0.427 AC XY: 31750 AN XY: 74292

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.446

Alfa AF: 0.475 Hom.: 2289

Bravo AF: 0.422

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.4
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2070668; hg19: chr11-116701153; COSMIC: COSV57138553; COSMIC: COSV57138553;