rs2070666

Positions:

• chr11-116830958-T-A
• chr11-116830958-T-C

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.179+62T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,348,786 control chromosomes in the GnomAD database, including 21,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (1715 hom., cov: 24)
  • Exomes 𝑓: 0.19 (19843 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

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=-0.89).
• BP6: Variant 11-116830958-T-A is Benign according to our data. Variant chr11-116830958-T-A is described in ClinVar as [Benign]. Clinvar id is 1183806.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116830958-T-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.179+62T>A		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.179+62T>A		intron_variant		1	NM_000040.3	P1
APOC3	ENST00000630701.1	c.233+62T>A		intron_variant		1
APOC3	ENST00000375345.3	c.233+62T>A		intron_variant		5
APOC3	ENST00000470144.1	n.211+62T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 20779 AN: 111264 Hom.: 1712 Cov.: 24

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.187 AC: 231788 AN: 1237458 Hom.: 19843 Cov.: 29 AF XY: 0.188 AC XY: 116044 AN XY: 616790

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.187 AC: 20806 AN: 111328 Hom.: 1715 Cov.: 24 AF XY: 0.193 AC XY: 10416 AN XY: 53918

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.206

Alfa AF: 0.0728 Hom.: 100

Bravo AF: 0.140

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

Apr 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2070666; hg19: chr11-116701674; COSMIC: COSV52636641; COSMIC: COSV52636641;