chr2-140274518-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_018557.3(LRP1B):c.13048C>G(p.Arg4350Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000333 in 1,612,306 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4350H) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00035 ( 0 hom. )
Consequence
LRP1B
NM_018557.3 missense
NM_018557.3 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 6.30
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, LRP1B
BS2
?
High AC in GnomAd at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP1B | NM_018557.3 | c.13048C>G | p.Arg4350Gly | missense_variant | 85/91 | ENST00000389484.8 | |
LRP1B | XM_017004341.2 | c.12658C>G | p.Arg4220Gly | missense_variant | 85/91 | ||
LRP1B | XM_017004342.1 | c.7900C>G | p.Arg2634Gly | missense_variant | 56/62 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP1B | ENST00000389484.8 | c.13048C>G | p.Arg4350Gly | missense_variant | 85/91 | 1 | NM_018557.3 | P1 | |
LRP1B | ENST00000437977.5 | c.1744C>G | p.Arg582Gly | missense_variant | 12/17 | 5 | |||
LRP1B | ENST00000442974.1 | c.244C>G | p.Arg82Gly | missense_variant | 2/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000198 AC: 30AN: 151806Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
30
AN:
151806
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000223 AC: 56AN: 250854Hom.: 0 AF XY: 0.000229 AC XY: 31AN XY: 135566
GnomAD3 exomes
AF:
AC:
56
AN:
250854
Hom.:
AF XY:
AC XY:
31
AN XY:
135566
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000347 AC: 507AN: 1460384Hom.: 0 Cov.: 30 AF XY: 0.000334 AC XY: 243AN XY: 726512
GnomAD4 exome
AF:
AC:
507
AN:
1460384
Hom.:
Cov.:
30
AF XY:
AC XY:
243
AN XY:
726512
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 151922Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74242
GnomAD4 genome
?
AF:
AC:
30
AN:
151922
Hom.:
Cov.:
33
AF XY:
AC XY:
11
AN XY:
74242
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
31
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2022 | The c.13048C>G (p.R4350G) alteration is located in exon 85 (coding exon 85) of the LRP1B gene. This alteration results from a C to G substitution at nucleotide position 13048, causing the arginine (R) at amino acid position 4350 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
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