rs2070667

Positions:

• chr11-116830953-G-A
• chr11-116830953-G-C
• chr11-116830953-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000227667.8(APOC3):​c.179+57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,182,366 control chromosomes in the GnomAD database, including 13,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5799 hom., cov: 23)
  • Exomes 𝑓: 0.087 (7726 hom.)
• Consequence: APOC3 ENST00000227667.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-116830953-G-A is Benign according to our data. Variant chr11-116830953-G-A is described in ClinVar as [Benign]. Clinvar id is 1244142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116830953-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC3	NM_000040.3	c.179+57G>A		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>A		intron_variant		1	NM_000040.3	ENSP00000227667	P1
APOC3	ENST00000630701.1	c.233+57G>A		intron_variant		1		ENSP00000486182
APOC3	ENST00000375345.3	c.233+57G>A		intron_variant		5		ENSP00000364494
APOC3	ENST00000470144.1	n.211+57G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 27556 AN: 111812 Hom.: 5791 Cov.: 23

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0820

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.0869 AC: 93031 AN: 1070452 Hom.: 7726 Cov.: 30 AF XY: 0.0835 AC XY: 44995 AN XY: 539122

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.0580

Gnomad4 ASJ exome AF: 0.0784

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.0452

Gnomad4 NFE exome AF: 0.0671

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.247 AC: 27606 AN: 111914 Hom.: 5799 Cov.: 23 AF XY: 0.247 AC XY: 13187 AN XY: 53406

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0950

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0229 Hom.: 22

Bravo AF: 0.212

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	10
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;