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GeneBe

2-140297947-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_018557.3(LRP1B):c.12828A>C(p.Ala4276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,612,388 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.64
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 -11 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=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-140297947-T-G is Benign according to our data. Variant chr2-140297947-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3039093.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=-4.64 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 195 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRP1BNM_018557.3 linkuse as main transcriptc.12828A>C p.Ala4276= synonymous_variant 84/91 ENST00000389484.8
LRP1BXM_017004341.2 linkuse as main transcriptc.12438A>C p.Ala4146= synonymous_variant 84/91
LRP1BXM_017004342.1 linkuse as main transcriptc.7680A>C p.Ala2560= synonymous_variant 55/62

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRP1BENST00000389484.8 linkuse as main transcriptc.12828A>C p.Ala4276= synonymous_variant 84/911 NM_018557.3 P1
LRP1BENST00000437977.5 linkuse as main transcriptc.1524A>C p.Ala508= synonymous_variant 11/175
LRP1BENST00000442974.1 linkuse as main transcriptc.24A>C p.Ala8= synonymous_variant 1/75

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00128
AC:
195
AN:
152182
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00229
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00142
AC:
355
AN:
250696
Hom.:
2
AF XY:
0.00140
AC XY:
190
AN XY:
135460
show subpopulations
Gnomad AFR exome
AF:
0.000370
Gnomad AMR exome
AF:
0.000493
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00162
Gnomad NFE exome
AF:
0.00253
Gnomad OTH exome
AF:
0.00180
GnomAD4 exome
AF:
0.00194
AC:
2833
AN:
1460088
Hom.:
6
Cov.:
31
AF XY:
0.00186
AC XY:
1350
AN XY:
726214
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.000403
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00174
Gnomad4 NFE exome
AF:
0.00237
Gnomad4 OTH exome
AF:
0.00136
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00128
AC:
195
AN:
152300
Hom.:
1
Cov.:
32
AF XY:
0.00128
AC XY:
95
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00229
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00185
Hom.:
1
Bravo
AF:
0.00113
EpiCase
AF:
0.00247
EpiControl
AF:
0.00137

ClinVar

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

Submissions by phenotype

LRP1B-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 21, 2019This variant is classified as likely 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
-0.85
Cadd
Benign
0.26
Dann
Benign
0.54

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: rs149487197; hg19: chr2-141055516; API