1-53250744-G-C

Variant summary

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

The NM_004631.5(LRP8):​c.2622C>G​(p.Asp874Glu) 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. 13/21 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: 31)

Consequence

LRP8
NM_004631.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.466
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12812346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRP8NM_004631.5 linkc.2622C>G p.Asp874Glu missense_variant Exon 17 of 19 ENST00000306052.12 NP_004622.2 Q14114-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRP8ENST00000306052.12 linkc.2622C>G p.Asp874Glu missense_variant Exon 17 of 19 1 NM_004631.5 ENSP00000303634.6 Q14114-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
2.6
DANN
Uncertain
0.98
DEOGEN2
Benign
0.072
T;.;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.80
T;T;.;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.1
L;L;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.67
N;N;N;N;N
REVEL
Benign
0.044
Sift
Benign
0.45
T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.011
B;B;B;B;B
Vest4
0.16
MutPred
0.23
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;.;.;
MVP
0.68
MPC
0.37
ClinPred
0.040
T
GERP RS
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.027
gMVP
0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-53716416; API