GeneBe

rs769448

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000041.4(APOE):​c.-23-280C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 17)
Failed GnomAD Quality Control

Consequence

APOE
NM_000041.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.685

Publications

13 publications found
Variant links:
Genes affected
APOE (HGNC:613): (apolipoprotein E) The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
APOE Gene-Disease associations (from GenCC):
  • Alzheimer disease 2
    Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hyperlipoproteinemia type 3
    Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
  • lipoprotein glomerulopathy
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp
  • sea-blue histiocyte syndrome
    Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOENM_000041.4 linkc.-23-280C>G intron_variant Intron 1 of 3 ENST00000252486.9 NP_000032.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOEENST00000252486.9 linkc.-23-280C>G intron_variant Intron 1 of 3 1 NM_000041.4 ENSP00000252486.3

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
67132
Hom.:
0
Cov.:
17
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
67132
Hom.:
0
Cov.:
17
AF XY:
0.00
AC XY:
0
AN XY:
30226
African (AFR)
AF:
0.00
AC:
0
AN:
16732
American (AMR)
AF:
0.00
AC:
0
AN:
4076
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1980
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2098
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1772
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
2020
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
86
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
37054
Other (OTH)
AF:
0.00
AC:
0
AN:
836
Alfa
AF:
0.00
Hom.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
3.2
DANN
Benign
0.73
PhyloP100
-0.69
PromoterAI
-0.012
Neutral

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

Other links and lift over

dbSNP: rs769448; hg19: chr19-45409579; API