Variant rs12691089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.419

Variant links:

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 links:

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]

APOC4-APOC2 links:

APOC4-APOC2 (HGNC:):

APOC4-APOC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033434033).

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOC4	NM_001646.3 linkuse as main transcript	c.155G>A	p.Gly52Asp	missense_variant	2/3	ENST00000592954.2	NP_001637.1	P55056
APOC4-APOC2	NR_037932.1 linkuse as main transcript	n.195G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOC4	ENST00000592954.2 linkuse as main transcript	c.155G>A	p.Gly52Asp	missense_variant	2/3	1	NM_001646.3	ENSP00000468236.1	P55056
APOC4-APOC2	ENST00000589057.5 linkuse as main transcript	c.155G>A	p.Gly52Asp	missense_variant	2/5	5		ENSP00000468139.1	K7ER74
APOC4	ENST00000591600.1 linkuse as main transcript	c.155G>A	p.Gly52Asp	missense_variant	2/2	3		ENSP00000466444.1	K7EMC3
APOC4-APOC2	ENST00000585685.5 linkuse as main transcript	n.155G>A		non_coding_transcript_exon_variant	2/6	5		ENSP00000467185.1

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

949

AN:

152156

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00658

AC XY:

848

AN XY:

128870

show subpopulations

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.:

Cov.:

AF XY:

0.00482

AC XY:

3489

AN XY:

724206

show subpopulations

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.:

Cov.:

AF XY:

0.00776

AC XY:

578

AN XY:

74452

show subpopulations

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.:

Bravo

AF:

0.00320

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00631

AC:

766

Asia WGS

AF:

0.000289

AC:

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

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

LIST_S2

Benign

0.44

.;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.011

B;.;.

Vest4

0.12

MVP

0.29

ClinPred

0.0021

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over