dbSNP rs5158: APOC4:c.77-828C>T (chr19-44943921-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.86

Publications

11 publications found

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:

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ACMG classification

Classification was made for transcript

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

Sel.	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	P55056
	APOC4-APOC2	NR_037932.1		n.117-828C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOC4	ENST00000592954.2	TSL:1 MANE Select	c.77-828C>T	intron	N/A	ENSP00000468236.1	P55056
APOC4-APOC2	ENST00000589057.5	TSL:5	c.77-828C>T	intron	N/A	ENSP00000468139.1	K7ER74
APOC4	ENST00000896758.1		c.77-807C>T	intron	N/A	ENSP00000566817.1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17235

AN:

152102

Hom.:

1173

Cov.:

show subpopulations

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.:

AF XY:

0.115

AC XY:

8555

AN XY:

74434

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9368

AN:

67996

Other (OTH)

AF:

0.101

AC:

212

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

779

1559

2338

3118

3897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.62

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over