11-116830500-G-A

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.-13-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,558,878 control chromosomes in the GnomAD database, including 2,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (1235 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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=-0.9).
• BP6: Variant 11-116830500-G-A is Benign according to our data. Variant chr11-116830500-G-A is described in ClinVar as [Benign]. Clinvar id is 1229152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.-13-70G>A		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-13-70G>A		intron_variant		1	NM_000040.3	P1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11298 AN: 152050 Hom.: 1365 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0540

GnomAD3 exomes AF: 0.0189 AC: 4359 AN: 230778 Hom.: 493 AF XY: 0.0140 AC XY: 1748 AN XY: 124972

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000346

Gnomad FIN exome AF: 0.0000517

Gnomad NFE exome AF: 0.000552

Gnomad OTH exome AF: 0.00649

GnomAD4 exome AF: 0.00778 AC: 10938 AN: 1406710 Hom.: 1235 Cov.: 27 AF XY: 0.00673 AC XY: 4724 AN XY: 701526

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0000784

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000644

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.000528

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0743 AC: 11307 AN: 152168 Hom.: 1366 Cov.: 32 AF XY: 0.0720 AC XY: 5355 AN XY: 74406

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0379 Hom.: 121

Bravo AF: 0.0863

Asia WGS AF: 0.00982 AC: 34 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

Mar 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.26
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs5143; hg19: chr11-116701216;