rs769449
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000041.4(APOE):c.43+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,460,964 control chromosomes in the GnomAD database, including 9,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.084 ( 699 hom., cov: 31)
Exomes 𝑓: 0.12 ( 9129 hom. )
Consequence
APOE
NM_000041.4 intron
NM_000041.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.335
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 19-44906745-G-A is Benign according to our data. Variant chr19-44906745-G-A is described in ClinVar as [Benign]. Clinvar id is 1264941.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44906745-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOE | NM_000041.4 | c.43+78G>A | intron_variant | ENST00000252486.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOE | ENST00000252486.9 | c.43+78G>A | intron_variant | 1 | NM_000041.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0839 AC: 12752AN: 151926Hom.: 693 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
12752
AN:
151926
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.116 AC: 151229AN: 1308920Hom.: 9129 Cov.: 20 AF XY: 0.114 AC XY: 75417AN XY: 658794
GnomAD4 exome
AF:
AC:
151229
AN:
1308920
Hom.:
Cov.:
20
AF XY:
AC XY:
75417
AN XY:
658794
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0840 AC: 12773AN: 152044Hom.: 699 Cov.: 31 AF XY: 0.0880 AC XY: 6534AN XY: 74292
GnomAD4 genome
?
AF:
AC:
12773
AN:
152044
Hom.:
Cov.:
31
AF XY:
AC XY:
6534
AN XY:
74292
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
446
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at