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rs35821928

chr2-140510004-G-Achr2-140510004-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_018557.3(LRP1B):c.8322C>T(p.Cys2774=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,613,798 control chromosomes in the GnomAD database, including 4,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.059 ( 355 hom., cov: 32)
Exomes 𝑓: 0.065 ( 3647 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130
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 -13 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=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-140510004-G-A is Benign according to our data. Variant chr2-140510004-G-A is described in ClinVar as [Benign]. Clinvar id is 3055616.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=-0.013 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 = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRP1BNM_018557.3 linkuse as main transcriptc.8322C>T p.Cys2774= synonymous_variant 52/91 ENST00000389484.8
LRP1BXM_017004341.2 linkuse as main transcriptc.7932C>T p.Cys2644= synonymous_variant 52/91
LRP1BXM_047444771.1 linkuse as main transcriptc.8433C>T p.Cys2811= synonymous_variant 52/77
LRP1BXM_017004342.1 linkuse as main transcriptc.3174C>T p.Cys1058= synonymous_variant 23/62

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRP1BENST00000389484.8 linkuse as main transcriptc.8322C>T p.Cys2774= synonymous_variant 52/911 NM_018557.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0592
AC:
8997
AN:
152082
Hom.:
355
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0278
Gnomad AMI
AF:
0.0198
Gnomad AMR
AF:
0.0614
Gnomad ASJ
AF:
0.0723
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0334
Gnomad FIN
AF:
0.0685
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0827
Gnomad OTH
AF:
0.0546
GnomAD3 exomes
AF:
0.0570
AC:
14317
AN:
251362
Hom.:
568
AF XY:
0.0579
AC XY:
7869
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.0285
Gnomad AMR exome
AF:
0.0359
Gnomad ASJ exome
AF:
0.0729
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.0344
Gnomad FIN exome
AF:
0.0716
Gnomad NFE exome
AF:
0.0782
Gnomad OTH exome
AF:
0.0623
GnomAD4 exome
AF:
0.0650
AC:
94952
AN:
1461598
Hom.:
3647
Cov.:
31
AF XY:
0.0652
AC XY:
47385
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.0256
Gnomad4 AMR exome
AF:
0.0371
Gnomad4 ASJ exome
AF:
0.0727
Gnomad4 EAS exome
AF:
0.000327
Gnomad4 SAS exome
AF:
0.0341
Gnomad4 FIN exome
AF:
0.0727
Gnomad4 NFE exome
AF:
0.0718
Gnomad4 OTH exome
AF:
0.0584
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0591
AC:
8996
AN:
152200
Hom.:
355
Cov.:
32
AF XY:
0.0588
AC XY:
4373
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0277
Gnomad4 AMR
AF:
0.0612
Gnomad4 ASJ
AF:
0.0723
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0332
Gnomad4 FIN
AF:
0.0685
Gnomad4 NFE
AF:
0.0828
Gnomad4 OTH
AF:
0.0545
Alfa
AF:
0.0719
Hom.:
231
Bravo
AF:
0.0543
Asia WGS
AF:
0.0160
AC:
56
AN:
3478
EpiCase
AF:
0.0748
EpiControl
AF:
0.0761

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 SciencesDec 16, 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
-0.39
Cadd
Benign
4.9
Dann
Benign
0.58

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: rs35821928; hg19: chr2-141267573; COSMIC: COSV67206921; API