Variant 19-44948399-T-G 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.-13-67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,349,646 control chromosomes in the GnomAD database, including 27,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3749 hom., cov: 31)

Exomes 𝑓: 0.19 ( 23865 hom. )

Consequence

APOC2
NM_000483.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

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=-0.85).

BP6

Variant 19-44948399-T-G is Benign according to our data. Variant chr19-44948399-T-G is described in ClinVar as [Benign]. Clinvar id is 1255025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44948399-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.302 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.-13-67T>G		intron_variant		ENST00000252490.7	NP_000474.2
APOC4-APOC2	NR_037932.1 linkuse as main transcript	n.1195-67T>G		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.-13-67T>G		intron_variant		2	NM_000483.5	ENSP00000252490	P1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32211

AN:

151376

Hom.:

3747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.191

AC:

229135

AN:

1198152

Hom.:

23865

Cov.:

AF XY:

0.195

AC XY:

118663

AN XY:

608428

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0696

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.213

AC:

32234

AN:

151494

Hom.:

3749

Cov.:

AF XY:

0.211

AC XY:

15647

AN XY:

74002

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0859

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.201

Hom.:

432

Bravo

AF:

0.218

Asia WGS

AF:

0.200

AC:

698

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.26

DANN

Benign

0.64

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