19-44948512-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_000483.5(APOC2):c.34G>A(p.Val12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V12V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

APOC2
NM_000483.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.914

Publications

6 publications found

Variant links:

Genes affected

APOC2 (HGNC:609): (apolipoprotein C2) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is secreted in plasma where it is a component of very low density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides and thus provides free fatty acids for cells. Mutations in this gene cause hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene. [provided by RefSeq, Mar 2011]

APOC2 links:

APOC4-APOC2 (HGNC:44426): (APOC4-APOC2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring apolipoprotein C-IV (APOC4) and apolipoprotein C-II (APOC2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

APOC4-APOC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075594783).

BP6

Variant 19-44948512-G-A is Benign according to our data. Variant chr19-44948512-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1530932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000584 (89/152274) while in subpopulation AMR AF = 0.000981 (15/15294). AF 95% confidence interval is 0.000664. There are 0 homozygotes in GnomAd4. There are 51 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000483.5. 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
	APOC2	NM_000483.5	MANE Select	c.34G>A	p.Val12Ile	missense	Exon 2 of 4	NP_000474.2
	APOC4-APOC2	NR_037932.1		n.1241G>A		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOC2	ENST00000252490.7	TSL:2 MANE Select	c.34G>A	p.Val12Ile	missense	Exon 2 of 4	ENSP00000252490.5	P02655
APOC4-APOC2	ENST00000589057.5	TSL:5	c.265G>A	p.Val89Ile	missense	Exon 3 of 5	ENSP00000468139.1	K7ER74
APOC2	ENST00000896555.1		c.34G>A	p.Val12Ile	missense	Exon 2 of 4	ENSP00000566614.1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000346

AC:

AN:

251484

AF XY:

0.000361

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000265

AC:

387

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

185

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33480

American (AMR)

AF:

0.000626

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00383

AC:

100

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000170

AC:

189

AN:

1111988

Other (OTH)

AF:

0.000497

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

111

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:

0.000584

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41568

American (AMR)

AF:

0.000981

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68016

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

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:

0.000548

Hom.:

Bravo

AF:

0.000669

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely 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

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.056

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.013

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.63

M_CAP

Benign

0.050

MetaRNN

Benign

0.0076

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.64

PhyloP100

-0.91

PROVEAN

Benign

-0.50

REVEL

Benign

0.090

Sift

Benign

0.40

Sift4G

Benign

0.33

Polyphen

0.0090

Vest4

0.088

MVP

0.16

MPC

0.15

ClinPred

0.0056

GERP RS

-2.0

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.33

Mutation Taster

=93/7

polymorphism

(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