rs5158

Variant names:

• chr19-44943921-C-T
• rs5158
• NM_001646.3:c.77-828C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001646.3(APOC4):​c.77-828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,220 control chromosomes in the GnomAD database, including 1,171 homozygotes. 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: 𝑓 0.11 (1171 hom., cov: 31)
• Consequence: APOC4 NM_001646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 11 publications found

Genes affected

APOC4 (HGNC:611): (apolipoprotein C4) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is thought to play a role in lipid metabolism. Polymorphisms in this gene may influence circulating lipid levels and may be associated with coronary artery disease risk. 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 downstream apolipoprotein C-II (APOC2) 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001646.3. 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
	APOC4	NM_001646.3	MANE Select	c.77-828C>T		intron	N/A	NP_001637.1
	APOC4-APOC2	NR_037932.1		n.117-828C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC4	ENST00000592954.2	TSL:1 MANE Select	c.77-828C>T		intron	N/A	ENSP00000468236.1
	APOC4-APOC2	ENST00000589057.5	TSL:5	c.77-828C>T		intron	N/A	ENSP00000468139.1
	APOC4	ENST00000591600.1	TSL:3	c.77-828C>T		intron	N/A	ENSP00000466444.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17235 AN: 152102 Hom.: 1173 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17223 AN: 152220 Hom.: 1171 Cov.: 31 AF XY: 0.115 AC XY: 8555 AN XY: 74434

African (AFR) AF: 0.0494 AC: 2053 AN: 41548

American (AMR) AF: 0.147 AC: 2251 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.103 AC: 532 AN: 5172

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4830

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9368 AN: 67996

Other (OTH) AF: 0.101 AC: 212 AN: 2108

Alfa AF: 0.134 Hom.: 1698

Bravo AF: 0.112

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.061
DANN	Benign	0.62
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs5158; hg19: chr19-45447178;