Variant chr19-44948363-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000483.5(APOC2):c.-13-103T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 969,836 control chromosomes in the GnomAD database, including 150,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 29001 hom., cov: 32)

Exomes 𝑓: 0.54 ( 121350 hom. )

Consequence

APOC2
NM_000483.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.277

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:):

APOC4-APOC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-44948363-T-A is Benign according to our data. Variant chr19-44948363-T-A is described in ClinVar as [Benign]. Clinvar id is 1232427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44948363-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC2	NM_000483.5 linkuse as main transcript	c.-13-103T>A		intron_variant		ENST00000252490.7	NP_000474.2
APOC4-APOC2	NR_037932.1 linkuse as main transcript	n.1195-103T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC2	ENST00000252490.7 linkuse as main transcript	c.-13-103T>A		intron_variant		2	NM_000483.5	ENSP00000252490	P1

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91693

AN:

151660

Hom.:

28952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.628

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.537

AC:

439614

AN:

818058

Hom.:

121350

Cov.:

AF XY:

0.538

AC XY:

231500

AN XY:

430558

show subpopulations

Gnomad4 AFR exome

AF:

0.766

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.486

Gnomad4 EAS exome

AF:

0.625

Gnomad4 SAS exome

AF:

0.622

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.551

GnomAD4 genome

AF:

0.605

AC:

91795

AN:

151778

Hom.:

29001

Cov.:

AF XY:

0.606

AC XY:

44981

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.478

Gnomad4 EAS

AF:

0.628

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.524

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.580

Alfa

AF:

0.568

Hom.:

3207

Bravo

AF:

0.623

Asia WGS

AF:

0.656

AC:

2282

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over