12-12175830-T-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002336.3(LRP6):c.1545+3980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,532 control chromosomes in the GnomAD database, including 14,327 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.39 ( 14327 hom., cov: 33)
Consequence
LRP6
NM_002336.3 intron
NM_002336.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0130
Publications
3 publications found
Genes affected
LRP6 (HGNC:6698): (LDL receptor related protein 6) This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]
BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP6 | ENST00000261349.9 | c.1545+3980A>G | intron_variant | Intron 7 of 22 | 1 | NM_002336.3 | ENSP00000261349.4 | |||
LRP6 | ENST00000543091.1 | c.1545+3980A>G | intron_variant | Intron 7 of 22 | 1 | ENSP00000442472.1 | ||||
LRP6 | ENST00000538239.5 | n.1137+3980A>G | intron_variant | Intron 6 of 23 | 1 | ENSP00000445083.1 | ||||
BCL2L14 | ENST00000298566.2 | n.*25-11475T>C | intron_variant | Intron 5 of 6 | 2 | ENSP00000298566.1 |
Frequencies
GnomAD3 genomes AF: 0.395 AC: 59838AN: 151414Hom.: 14340 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
59838
AN:
151414
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:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.395 AC: 59831AN: 151532Hom.: 14327 Cov.: 33 AF XY: 0.409 AC XY: 30288AN XY: 74070 show subpopulations
GnomAD4 genome
AF:
AC:
59831
AN:
151532
Hom.:
Cov.:
33
AF XY:
AC XY:
30288
AN XY:
74070
show subpopulations
African (AFR)
AF:
AC:
4998
AN:
41506
American (AMR)
AF:
AC:
7648
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
AC:
1542
AN:
3466
East Asian (EAS)
AF:
AC:
3735
AN:
5178
South Asian (SAS)
AF:
AC:
3047
AN:
4822
European-Finnish (FIN)
AF:
AC:
5627
AN:
10174
Middle Eastern (MID)
AF:
AC:
109
AN:
292
European-Non Finnish (NFE)
AF:
AC:
31906
AN:
67824
Other (OTH)
AF:
AC:
874
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1635
3270
4906
6541
8176
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
566
1132
1698
2264
2830
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2209
AN:
3470
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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