Genetic Variant APOC3:c.-13-62C>T (chr11-116830508-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000040.3(APOC3):c.-13-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,589,308 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 101 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 83 hom. )

Consequence

APOC3
NM_000040.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.772

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 -20 ACMG points.

BP4

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

BP6

Variant 11-116830508-C-T is Benign according to our data. Variant chr11-116830508-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 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.-13-62C>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.-13-62C>T	intron	N/A	ENSP00000227667.2	P02656
APOC3	ENST00000375345.3	TSL:5	c.-21C>T	5_prime_UTR	Exon 2 of 4	ENSP00000364494.1	B0YIW2
APOC3	ENST00000863804.1		c.-13-62C>T	intron	N/A	ENSP00000533863.1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2777

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00460

AC:

1100

AN:

239090

AF XY:

0.00351

show subpopulations

Gnomad AFR exome

AF:

0.0607

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.00202

AC:

2907

AN:

1437032

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1274

AN XY:

715714

show subpopulations

African (AFR)

AF:

0.0633

AC:

2092

AN:

33060

American (AMR)

AF:

0.00357

AC:

156

AN:

43730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25784

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.000165

AC:

AN:

84966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51704

Middle Eastern (MID)

AF:

0.00773

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000284

AC:

310

AN:

1093034

Other (OTH)

AF:

0.00488

AC:

291

AN:

59584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

164

329

493

658

822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0184

AC:

2800

AN:

152276

Hom.:

101

Cov.:

AF XY:

0.0179

AC XY:

1334

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0635

AC:

2639

AN:

41542

American (AMR)

AF:

0.00725

AC:

111

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68000

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

119

238

356

475

594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0120

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.57

PhyloP100

-0.77

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=287/13

polymorphism (auto)

(source)

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

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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