19-44948185-A-G

Position:

• chr19-44948185-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000483.5(APOC2):​c.-13-281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 313,086 control chromosomes in the GnomAD database, including 41,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21621 hom., cov: 32)
  • Exomes 𝑓: 0.49 (20048 hom.)
• Consequence: APOC2 NM_000483.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.36

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]

APOC4-APOC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-44948185-A-G is Benign according to our data. Variant chr19-44948185-A-G is described in ClinVar as [Benign]. Clinvar id is 1281172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44948185-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC2	NM_000483.5	c.-13-281A>G		intron_variant		ENST00000252490.7	NP_000474.2
APOC4-APOC2	NR_037932.1	n.1195-281A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC2	ENST00000252490.7	c.-13-281A>G		intron_variant		2	NM_000483.5	ENSP00000252490	P1
APOC2	ENST00000590360.2	c.-13-281A>G		intron_variant		3		ENSP00000466775	P1
APOC2	ENST00000591597.5	c.-13-281A>G		intron_variant		5		ENSP00000476835
APOC2	ENST00000592257.5	c.-13-281A>G		intron_variant		3		ENSP00000477261

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79725 AN: 151704 Hom.: 21588 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.489 AC: 78838 AN: 161264 Hom.: 20048 AF XY: 0.496 AC XY: 43320 AN XY: 87406

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.526 AC: 79808 AN: 151822 Hom.: 21621 Cov.: 32 AF XY: 0.528 AC XY: 39167 AN XY: 74198

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.504

Alfa AF: 0.505 Hom.: 2479

Bravo AF: 0.534

Asia WGS AF: 0.580 AC: 2016 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	-0.97
CADD	Benign	0.047
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs7256684; hg19: chr19-45451442;