rs2070666

Variant names:

• chr11-116830958-T-A
• rs2070666
• NM_000040.3:c.179+62T>A

Your query was ambiguous. Multiple possible variants found:

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

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.17
• Publications: 17 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=-0.89).
• BP6: Variant 11-116830958-T-A is Benign according to our data. Variant chr11-116830958-T-A is described in ClinVar as Benign. ClinVar VariationId is 1183806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
APOC3	NM_000040.3	c.179+62T>A		intron_variant	Intron 3 of 3	ENST00000227667.8	NP_000031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC3	ENST00000227667.8	c.179+62T>A		intron_variant	Intron 3 of 3	1	NM_000040.3	ENSP00000227667.2

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

African (AFR) AF: 0.0602 AC: 1621 AN: 26906

American (AMR) AF: 0.279 AC: 10920 AN: 39204

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3997 AN: 21030

East Asian (EAS) AF: 0.323 AC: 10311 AN: 31880

South Asian (SAS) AF: 0.199 AC: 16036 AN: 80448

European-Finnish (FIN) AF: 0.247 AC: 9060 AN: 36632

Middle Eastern (MID) AF: 0.215 AC: 841 AN: 3904

European-Non Finnish (NFE) AF: 0.179 AC: 169413 AN: 948060

Other (OTH) AF: 0.194 AC: 9589 AN: 49394

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

African (AFR) AF: 0.0805 AC: 2127 AN: 26414

American (AMR) AF: 0.257 AC: 2906 AN: 11298

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 533 AN: 2840

East Asian (EAS) AF: 0.338 AC: 1341 AN: 3964

South Asian (SAS) AF: 0.247 AC: 885 AN: 3576

European-Finnish (FIN) AF: 0.312 AC: 2042 AN: 6548

Middle Eastern (MID) AF: 0.180 AC: 45 AN: 250

European-Non Finnish (NFE) AF: 0.193 AC: 10486 AN: 54210

Other (OTH) AF: 0.206 AC: 319 AN: 1548

Alfa AF: 0.0728 Hom.: 100

Bravo AF: 0.140

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.83
PhyloP100		-2.2
PromoterAI		-0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070666; hg19: chr11-116701674; COSMIC: COSV52636641; COSMIC: COSV52636641;