rs5127

Variant names:

• chr19-44949437-G-T
• rs5127
• NM_000483.5:c.*188G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000483.5(APOC2):​c.*188G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 474,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: APOC2 NM_000483.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 8 publications found

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:44426): (APOC4-APOC2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring apolipoprotein C-IV (APOC4) and apolipoprotein C-II (APOC2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000483.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC2	NM_000483.5	MANE Select	c.*188G>T		3_prime_UTR	Exon 4 of 4	NP_000474.2
	APOC4-APOC2	NR_037932.1		n.1701G>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC2	ENST00000252490.7	TSL:2 MANE Select	c.*188G>T		3_prime_UTR	Exon 4 of 4	ENSP00000252490.5
	APOC4-APOC2	ENST00000585685.5	TSL:5	n.*1277G>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000467185.1
	APOC2	ENST00000590360.2	TSL:3	c.*188G>T		3_prime_UTR	Exon 4 of 4	ENSP00000466775.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 1 AN: 474804 Hom.: 0 Cov.: 4 AF XY: 0.00000395 AC XY: 1 AN XY: 253130

African (AFR) AF: 0.00 AC: 0 AN: 13598

American (AMR) AF: 0.00 AC: 0 AN: 27116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15078

East Asian (EAS) AF: 0.00 AC: 0 AN: 30298

South Asian (SAS) AF: 0.00 AC: 0 AN: 50768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2018

European-Non Finnish (NFE) AF: 0.00000358 AC: 1 AN: 279144

Other (OTH) AF: 0.00 AC: 0 AN: 26770

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.50
DANN	Benign	0.72
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs5127; hg19: chr19-45452694;