rs5174
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004631.5(LRP8):c.2855G>T(p.Arg952Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R952Q) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LRP8
NM_004631.5 missense, splice_region
NM_004631.5 missense, splice_region
Scores
6
7
6
Splicing: ADA: 0.9750
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.18
Genes affected
LRP8 (HGNC:6700): (LDL receptor related protein 8) This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LRP8 | NM_004631.5 | c.2855G>T | p.Arg952Leu | missense_variant, splice_region_variant | Exon 19 of 19 | ENST00000306052.12 | NP_004622.2 | |
| LRP8 | NM_001018054.3 | c.2678G>T | p.Arg893Leu | missense_variant, splice_region_variant | Exon 18 of 18 | NP_001018064.1 | ||
| LRP8 | NM_033300.4 | c.2345G>T | p.Arg782Leu | missense_variant, splice_region_variant | Exon 17 of 17 | NP_150643.2 | ||
| LRP8 | NM_017522.5 | c.2066G>T | p.Arg689Leu | missense_variant, splice_region_variant | Exon 16 of 16 | NP_059992.3 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1443254Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 717630
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1443254
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
717630
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;.;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;D;D;D;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
N;.;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;D;D;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;T;T;D
Sift4G
Pathogenic
D;T;T;T;D
Polyphen
D;B;P;D;D
Vest4
MutPred
Gain of sheet (P = 0.0344);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at