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GeneBe

2-140274519-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_018557.3(LRP1B):c.13047G>A(p.Thr4349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,611,552 control chromosomes in the GnomAD database, including 348,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 24585 hom., cov: 32)
Exomes 𝑓: 0.66 ( 323906 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.288
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-140274519-C-T is Benign according to our data. Variant chr2-140274519-C-T is described in ClinVar as [Benign]. Clinvar id is 3060762.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.288 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRP1BNM_018557.3 linkuse as main transcriptc.13047G>A p.Thr4349= synonymous_variant 85/91 ENST00000389484.8
LRP1BXM_017004341.2 linkuse as main transcriptc.12657G>A p.Thr4219= synonymous_variant 85/91
LRP1BXM_017004342.1 linkuse as main transcriptc.7899G>A p.Thr2633= synonymous_variant 56/62

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRP1BENST00000389484.8 linkuse as main transcriptc.13047G>A p.Thr4349= synonymous_variant 85/911 NM_018557.3 P1
LRP1BENST00000437977.5 linkuse as main transcriptc.1743G>A p.Thr581= synonymous_variant 12/175
LRP1BENST00000442974.1 linkuse as main transcriptc.243G>A p.Thr81= synonymous_variant 2/75

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.536
AC:
81215
AN:
151616
Hom.:
24588
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.238
Gnomad AMI
AF:
0.725
Gnomad AMR
AF:
0.536
Gnomad ASJ
AF:
0.536
Gnomad EAS
AF:
0.673
Gnomad SAS
AF:
0.552
Gnomad FIN
AF:
0.702
Gnomad MID
AF:
0.547
Gnomad NFE
AF:
0.676
Gnomad OTH
AF:
0.554
GnomAD3 exomes
AF:
0.608
AC:
152554
AN:
250726
Hom.:
48288
AF XY:
0.615
AC XY:
83369
AN XY:
135500
show subpopulations
Gnomad AFR exome
AF:
0.232
Gnomad AMR exome
AF:
0.534
Gnomad ASJ exome
AF:
0.518
Gnomad EAS exome
AF:
0.685
Gnomad SAS exome
AF:
0.577
Gnomad FIN exome
AF:
0.689
Gnomad NFE exome
AF:
0.673
Gnomad OTH exome
AF:
0.614
GnomAD4 exome
AF:
0.660
AC:
963582
AN:
1459820
Hom.:
323906
Cov.:
42
AF XY:
0.659
AC XY:
478315
AN XY:
726262
show subpopulations
Gnomad4 AFR exome
AF:
0.223
Gnomad4 AMR exome
AF:
0.537
Gnomad4 ASJ exome
AF:
0.525
Gnomad4 EAS exome
AF:
0.669
Gnomad4 SAS exome
AF:
0.580
Gnomad4 FIN exome
AF:
0.681
Gnomad4 NFE exome
AF:
0.689
Gnomad4 OTH exome
AF:
0.627
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.535
AC:
81230
AN:
151732
Hom.:
24585
Cov.:
32
AF XY:
0.537
AC XY:
39771
AN XY:
74130
show subpopulations
Gnomad4 AFR
AF:
0.238
Gnomad4 AMR
AF:
0.536
Gnomad4 ASJ
AF:
0.536
Gnomad4 EAS
AF:
0.674
Gnomad4 SAS
AF:
0.554
Gnomad4 FIN
AF:
0.702
Gnomad4 NFE
AF:
0.676
Gnomad4 OTH
AF:
0.547
Alfa
AF:
0.603
Hom.:
18139
Bravo
AF:
0.512
Asia WGS
AF:
0.563
AC:
1954
AN:
3476
EpiCase
AF:
0.663
EpiControl
AF:
0.657

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

LRP1B-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
7.8
Dann
Benign
0.61

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: rs1386356; hg19: chr2-141032088; COSMIC: COSV67186048; API