rs12691089

chr19-44944827-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001646.3(APOC4):c.155G>A(p.Gly52Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,608,914 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0062 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (53 hom.)
• Consequence: APOC4 NM_001646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033434033).
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC4	NM_001646.3	c.155G>A	p.Gly52Asp	missense_variant	2/3	ENST00000592954.2
APOC4-APOC2	NR_037932.1	n.195G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC4	ENST00000592954.2	c.155G>A	p.Gly52Asp	missense_variant	2/3	1	NM_001646.3	P1
APOC4	ENST00000591600.1	c.155G>A	p.Gly52Asp	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 949 AN: 152156 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00657 AC: 1568 AN: 238704 Hom.: 19 AF XY: 0.00658 AC XY: 848 AN XY: 128870

Gnomad AFR exome AF: 0.000393

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00849

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00116

Gnomad FIN exome AF: 0.0339

Gnomad NFE exome AF: 0.00584

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00472 AC: 6870 AN: 1456640 Hom.: 53 Cov.: 33 AF XY: 0.00482 AC XY: 3489 AN XY: 724206

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00970

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.0336

Gnomad4 NFE exome AF: 0.00390

Gnomad4 OTH exome AF: 0.00438

GnomAD4 genome AF: 0.00623 AC: 949 AN: 152274 Hom.: 6 Cov.: 31 AF XY: 0.00776 AC XY: 578 AN XY: 74452

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00432

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.00578

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00516 Hom.: 2

Bravo AF: 0.00320

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00453 AC: 39

ExAC AF: 0.00631 AC: 766

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	2.3
Dann	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
Sift4G	Benign	0.14	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.12
MVP		0.29
ClinPred		0.0021	T
GERP RS		1.3
Varity_R		0.044
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12691089; hg19: chr19-45448084;