rs11542030

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000041.4(APOE):​c.614A>G​(p.Gln205Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

APOE
NM_000041.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.452
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26063).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOENM_000041.4 linkc.614A>G p.Gln205Arg missense_variant Exon 4 of 4 ENST00000252486.9 NP_000032.1 P02649A0A0S2Z3D5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOEENST00000252486.9 linkc.614A>G p.Gln205Arg missense_variant Exon 4 of 4 1 NM_000041.4 ENSP00000252486.3 P02649
APOEENST00000425718.1 linkc.614A>G p.Gln205Arg missense_variant Exon 3 of 3 1 ENSP00000410423.1 E7ERP7
APOEENST00000434152.5 linkc.692A>G p.Gln231Arg missense_variant Exon 4 of 4 2 ENSP00000413653.2 H0Y7L5
APOEENST00000446996.5 linkc.614A>G p.Gln205Arg missense_variant Exon 4 of 4 2 ENSP00000413135.1 E9PEV4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1316478
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
646710
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Benign
0.93
DEOGEN2
Benign
0.19
T;T;.;.
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.52
T;T;T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.2
L;.;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.9
N;N;.;N
REVEL
Benign
0.079
Sift
Benign
0.092
T;T;.;T
Sift4G
Benign
0.25
T;T;T;T
Polyphen
0.0040
B;.;.;.
Vest4
0.11
MutPred
0.69
Gain of methylation at Q205 (P = 0.0181);Gain of methylation at Q205 (P = 0.0181);.;Gain of methylation at Q205 (P = 0.0181);
MVP
0.90
MPC
0.73
ClinPred
0.075
T
GERP RS
1.6
Varity_R
0.058
gMVP
0.39

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

LitVar

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

Other links and lift over

dbSNP: rs11542030; hg19: chr19-45412167; API