rs267606662
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_000041.4(APOE):c.508G>C(p.Ala170Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
APOE
NM_000041.4 missense
NM_000041.4 missense
Scores
1
7
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0480
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
In a helix (size 31) in uniprot entity APOE_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_000041.4
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32213235).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOE | NM_000041.4 | c.508G>C | p.Ala170Pro | missense_variant | 4/4 | ENST00000252486.9 | NP_000032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOE | ENST00000252486.9 | c.508G>C | p.Ala170Pro | missense_variant | 4/4 | 1 | NM_000041.4 | ENSP00000252486 | P1 | |
APOE | ENST00000425718.1 | c.508G>C | p.Ala170Pro | missense_variant | 3/3 | 1 | ENSP00000410423 | |||
APOE | ENST00000434152.5 | c.586G>C | p.Ala196Pro | missense_variant | 4/4 | 2 | ENSP00000413653 | |||
APOE | ENST00000446996.5 | c.508G>C | p.Ala170Pro | missense_variant | 4/4 | 2 | ENSP00000413135 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Uncertain
Sift
Uncertain
D;D;.;D
Sift4G
Benign
T;T;D;T
Polyphen
D;.;.;.
Vest4
MutPred
Gain of ubiquitination at K175 (P = 0.0516);Gain of ubiquitination at K175 (P = 0.0516);.;Gain of ubiquitination at K175 (P = 0.0516);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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