19-44948277-T-G

Position:

• chr19-44948277-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000483.5(APOC2):​c.-13-189T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 599,928 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (2 hom.)
• Consequence: APOC2 NM_000483.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

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=-0.79).
• BP6: Variant 19-44948277-T-G is Benign according to our data. Variant chr19-44948277-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1254202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00572 (863/150800) while in subpopulation AFR AF= 0.0196 (805/41026). AF 95% confidence interval is 0.0185. There are 9 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC2	NM_000483.5	c.-13-189T>G		intron_variant		ENST00000252490.7	NP_000474.2
APOC4-APOC2	NR_037932.1	n.1195-189T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOC2	ENST00000252490.7	c.-13-189T>G		intron_variant		2	NM_000483.5	ENSP00000252490	P1

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 857 AN: 150684 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00218

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000637

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00532

GnomAD4 exome AF: 0.000877 AC: 394 AN: 449128 Hom.: 2 Cov.: 3 AF XY: 0.000812 AC XY: 194 AN XY: 239008

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.00149

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000341

Gnomad4 SAS exome AF: 0.000386

Gnomad4 FIN exome AF: 0.0000294

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00572 AC: 863 AN: 150800 Hom.: 9 Cov.: 33 AF XY: 0.00565 AC XY: 416 AN XY: 73612

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.00218

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000638

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.00526

Alfa AF: 0.00437 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12721060; hg19: chr19-45451534;