19-44948391-C-G

Position:

• chr19-44948391-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000483.5(APOC2):​c.-13-75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,278,286 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (15 hom.)
• Consequence: APOC2 NM_000483.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.174

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-44948391-C-G is Benign according to our data. Variant chr19-44948391-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1189660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1621/152232) while in subpopulation AFR AF= 0.0337 (1401/41524). AF 95% confidence interval is 0.0323. There are 31 homozygotes in gnomad4. There are 769 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC2	NM_000483.5	c.-13-75C>G		intron_variant		ENST00000252490.7
APOC4-APOC2	NR_037932.1	n.1195-75C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC2	ENST00000252490.7	c.-13-75C>G		intron_variant		2	NM_000483.5	P1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1617 AN: 152114 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00866

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00149 AC: 1678 AN: 1126054 Hom.: 15 Cov.: 16 AF XY: 0.00137 AC XY: 789 AN XY: 575368

Gnomad4 AFR exome AF: 0.0337

Gnomad4 AMR exome AF: 0.00290

Gnomad4 ASJ exome AF: 0.00842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000634

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00441

GnomAD4 genome AF: 0.0106 AC: 1621 AN: 152232 Hom.: 31 Cov.: 32 AF XY: 0.0103 AC XY: 769 AN XY: 74430

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.00864

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.0129

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.49
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

Other links and lift over

dbSNP: rs12709887; hg19: chr19-45451648;