NM_000040.3:c.-13-164C>G

Variant names:

• chr11-116830406-C-G
• rs2070669
• NM_000040.3:c.-13-164C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.310
• Publications: 15 publications found

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]

APOC3 Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1250696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	NM_000040.3	MANE Select	c.-13-164C>G		intron	N/A	NP_000031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	ENST00000227667.8	TSL:1 MANE Select	c.-13-164C>G		intron	N/A	ENSP00000227667.2
	APOC3	ENST00000375345.3	TSL:5	c.-36-87C>G		intron	N/A	ENSP00000364494.1
	APOC3	ENST00000433777.5	TSL:5	c.-13-164C>G		intron	N/A	ENSP00000410614.1

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

African (AFR) AF: 0.189 AC: 3002 AN: 15868

American (AMR) AF: 0.631 AC: 18711 AN: 29652

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 11038 AN: 17188

East Asian (EAS) AF: 0.527 AC: 16798 AN: 31900

South Asian (SAS) AF: 0.509 AC: 28799 AN: 56556

European-Finnish (FIN) AF: 0.695 AC: 22276 AN: 32046

Middle Eastern (MID) AF: 0.560 AC: 1339 AN: 2392

European-Non Finnish (NFE) AF: 0.705 AC: 254916 AN: 361380

Other (OTH) AF: 0.627 AC: 19147 AN: 30556

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

African (AFR) AF: 0.198 AC: 8217 AN: 41460

American (AMR) AF: 0.579 AC: 8845 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3468

East Asian (EAS) AF: 0.551 AC: 2833 AN: 5138

South Asian (SAS) AF: 0.504 AC: 2430 AN: 4818

European-Finnish (FIN) AF: 0.687 AC: 7275 AN: 10592

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47406 AN: 67902

Other (OTH) AF: 0.561 AC: 1182 AN: 2106

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.31
PromoterAI		-0.0083	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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