rs12721109

Variant names:

• chr19-44943964-G-A
• rs12721109
• NM_001646.3:c.77-785G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001646.3(APOC4):​c.77-785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 152,300 control chromosomes in the GnomAD database, including 21 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 0.013 (21 hom., cov: 31)
• Consequence: APOC4 NM_001646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 19 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=-0.95).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0131 (1994/152300) while in subpopulation NFE AF = 0.0223 (1514/68026). AF 95% confidence interval is 0.0213. There are 21 homozygotes in GnomAd4. There are 880 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC4	NM_001646.3	c.77-785G>A		intron_variant	Intron 1 of 2	ENST00000592954.2	NP_001637.1
APOC4-APOC2	NR_037932.1	n.117-785G>A		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC4	ENST00000592954.2	c.77-785G>A		intron_variant	Intron 1 of 2	1	NM_001646.3	ENSP00000468236.1
APOC4-APOC2	ENST00000589057.5	c.77-785G>A		intron_variant	Intron 1 of 4	5		ENSP00000468139.1
APOC4	ENST00000591600.1	c.77-785G>A		intron_variant	Intron 1 of 1	3		ENSP00000466444.1
APOC4-APOC2	ENST00000585685.5	n.77-785G>A		intron_variant	Intron 1 of 5	5		ENSP00000467185.1

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1996 AN: 152182 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.00717

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

GnomAD4 genome AF: 0.0131 AC: 1994 AN: 152300 Hom.: 21 Cov.: 31 AF XY: 0.0118 AC XY: 880 AN XY: 74468

African (AFR) AF: 0.00394 AC: 164 AN: 41574

American (AMR) AF: 0.00321 AC: 49 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1514 AN: 68026

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.0212 Hom.: 30

Bravo AF: 0.0122

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.73
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs12721109; hg19: chr19-45447221;