11-116830406-C-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.-13-164C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 729,516 control chromosomes in the GnomAD database, including 151,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (25277 hom., cov: 32)
  • Exomes 𝑓: 0.65 (126200 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310

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=-0.83).
• BP6: Variant 11-116830406-C-G is Benign according to our data. Variant chr11-116830406-C-G is described in ClinVar as [Benign]. Clinvar id is 1250696.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116830406-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.-13-164C>G		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-13-164C>G		intron_variant		1	NM_000040.3	P1
APOC3	ENST00000375345.3	c.-36-87C>G		intron_variant		5
APOC3	ENST00000433777.5	c.-13-164C>G		intron_variant		5
APOC3	ENST00000470144.1	n.20-164C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81193 AN: 151860 Hom.: 25285 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.651 AC: 376026 AN: 577538 Hom.: 126200 AF XY: 0.644 AC XY: 195261 AN XY: 303110

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.534 AC: 81206 AN: 151978 Hom.: 25277 Cov.: 32 AF XY: 0.531 AC XY: 39434 AN XY: 74288

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.561

Alfa AF: 0.466 Hom.: 1530

Bravo AF: 0.519

Asia WGS AF: 0.490 AC: 1708 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	-0.83
Cadd	Benign	2.3
Dann	Benign	0.45

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: rs2070669; hg19: chr11-116701122; COSMIC: COSV57138413; COSMIC: COSV57138413;