rs2070667

Variant names:

• chr11-116830953-G-A
• rs2070667
• NM_000040.3:c.179+57G>A

Your query was ambiguous. Multiple possible variants found:

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

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+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 NM_000040.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.182
• 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=-0.85).
• BP6: Variant 11-116830953-G-A is Benign according to our data. Variant chr11-116830953-G-A is described in ClinVar as Benign. ClinVar VariationId is 1244142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	NM_000040.3	MANE Select	c.179+57G>A		intron	N/A	NP_000031.1	A3KPE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	ENST00000227667.8	TSL:1 MANE Select	c.179+57G>A		intron	N/A	ENSP00000227667.2	P02656
	APOC3	ENST00000630701.1	TSL:1	c.233+57G>A		intron	N/A	ENSP00000486182.1	B0YIW2
	APOC3	ENST00000863804.1		c.236+57G>A		intron	N/A	ENSP00000533863.1

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

African (AFR) AF: 0.599 AC: 18596 AN: 31038

American (AMR) AF: 0.0580 AC: 2273 AN: 39198

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 1502 AN: 19160

East Asian (EAS) AF: 0.178 AC: 5461 AN: 30642

South Asian (SAS) AF: 0.0667 AC: 5196 AN: 77900

European-Finnish (FIN) AF: 0.0452 AC: 1575 AN: 34882

Middle Eastern (MID) AF: 0.0814 AC: 297 AN: 3650

European-Non Finnish (NFE) AF: 0.0671 AC: 53015 AN: 789628

Other (OTH) AF: 0.115 AC: 5116 AN: 44354

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

African (AFR) AF: 0.578 AC: 21039 AN: 36372

American (AMR) AF: 0.140 AC: 1390 AN: 9936

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 162 AN: 2566

East Asian (EAS) AF: 0.176 AC: 654 AN: 3726

South Asian (SAS) AF: 0.0950 AC: 307 AN: 3230

European-Finnish (FIN) AF: 0.0573 AC: 278 AN: 4854

Middle Eastern (MID) AF: 0.0901 AC: 20 AN: 222

European-Non Finnish (NFE) AF: 0.0703 AC: 3441 AN: 48924

Other (OTH) AF: 0.207 AC: 308 AN: 1488

Alfa AF: 0.0229 Hom.: 22

Bravo AF: 0.212

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		0.18
PromoterAI		-0.0027	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)		0.0		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: rs2070667; hg19: chr11-116701669;