rs193921022

Variant summary

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

The NM_018557.3(LRP1B):​c.6648G>T​(p.Glu2216Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

LRP1B
NM_018557.3 missense

Scores

8
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.121
Variant links:
Genes affected
LRP1B (HGNC:6693): (LDL receptor related protein 1B) This gene encodes a member of the low density lipoprotein (LDL) receptor family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands. Disruption of this gene has been reported in several types of cancer. [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=0.17271784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRP1BNM_018557.3 linkuse as main transcriptc.6648G>T p.Glu2216Asp missense_variant 41/91 ENST00000389484.8 NP_061027.2
LRP1BXM_017004341.2 linkuse as main transcriptc.6258G>T p.Glu2086Asp missense_variant 41/91 XP_016859830.1
LRP1BXM_047444771.1 linkuse as main transcriptc.6759G>T p.Glu2253Asp missense_variant 41/77 XP_047300727.1
LRP1BXM_017004342.1 linkuse as main transcriptc.1500G>T p.Glu500Asp missense_variant 12/62 XP_016859831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRP1BENST00000389484.8 linkuse as main transcriptc.6648G>T p.Glu2216Asp missense_variant 41/911 NM_018557.3 ENSP00000374135 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyScience for Life laboratory, Karolinska Institutet-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Benign
-0.0054
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.17
T
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.68
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.31
Sift
Uncertain
0.024
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.083
B
Vest4
0.43
MutPred
0.20
Loss of loop (P = 0.1242);
MVP
0.51
MPC
0.25
ClinPred
0.76
D
GERP RS
1.5
Varity_R
0.22
gMVP
0.53

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: rs193921022; hg19: chr2-141457970; COSMIC: COSV67269595; API