Genetic Variant APOC3:c.-13-83C>T (chr11-116830487-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000040.3(APOC3):c.-13-83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000638 in 1,469,776 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 4 hom. )

Consequence

APOC3
NM_000040.3 intron

Scores

Splicing: ADA: 0.00005056

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.843

Publications

0 publications found

Variant links:

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

APOC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-116830487-C-T is Benign according to our data. Variant chr11-116830487-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1207053.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 481 AD gene.

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.-13-83C>T		intron	N/A	NP_000031.1	A3KPE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOC3	ENST00000227667.8	TSL:1 MANE Select	c.-13-83C>T	intron	N/A	ENSP00000227667.2	P02656
APOC3	ENST00000863804.1		c.-13-83C>T	intron	N/A	ENSP00000533863.1
APOC3	ENST00000375345.3	TSL:5	c.-36-6C>T	splice_region intron	N/A	ENSP00000364494.1	B0YIW2

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

480

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000697

AC:

147

AN:

210792

AF XY:

0.000492

show subpopulations

Gnomad AFR exome

AF:

0.00947

Gnomad AMR exome

AF:

0.000403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000646

Gnomad OTH exome

AF:

0.000561

GnomAD4 exome

AF:

0.000347

AC:

457

AN:

1317466

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

208

AN XY:

659398

show subpopulations

African (AFR)

AF:

0.0114

AC:

350

AN:

30784

American (AMR)

AF:

0.000647

AC:

AN:

40172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24840

East Asian (EAS)

AF:

0.00

AC:

AN:

38484

South Asian (SAS)

AF:

0.0000370

AC:

AN:

81118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48130

Middle Eastern (MID)

AF:

0.000754

AC:

AN:

5302

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

993006

Other (OTH)

AF:

0.000719

AC:

AN:

55630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00316

AC:

481

AN:

152310

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0109

AC:

454

AN:

41570

American (AMR)

AF:

0.00124

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00360

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.36

PhyloP100

-0.84

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over