12-12223531-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002336.3(LRP6):​c.450-20131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,084 control chromosomes in the GnomAD database, including 14,485 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 ( 14485 hom., cov: 32)

Consequence

LRP6
NM_002336.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.144
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRP6NM_002336.3 linkc.450-20131T>C intron_variant Intron 2 of 22 ENST00000261349.9 NP_002327.2 O75581

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRP6ENST00000261349.9 linkc.450-20131T>C intron_variant Intron 2 of 22 1 NM_002336.3 ENSP00000261349.4 O75581
LRP6ENST00000543091.1 linkc.450-20131T>C intron_variant Intron 2 of 22 1 ENSP00000442472.1 F5H7J9
LRP6ENST00000538239.5 linkn.42-20131T>C intron_variant Intron 1 of 23 1 ENSP00000445083.1 H0YGW5
LRP6ENST00000535731.1 linkc.-4-20131T>C intron_variant Intron 1 of 2 3 ENSP00000439765.1 F5H0Z3

Frequencies

GnomAD3 genomes
AF:
0.394
AC:
59818
AN:
151966
Hom.:
14501
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.103
Gnomad AMI
AF:
0.399
Gnomad AMR
AF:
0.505
Gnomad ASJ
AF:
0.424
Gnomad EAS
AF:
0.704
Gnomad SAS
AF:
0.553
Gnomad FIN
AF:
0.572
Gnomad MID
AF:
0.396
Gnomad NFE
AF:
0.480
Gnomad OTH
AF:
0.416
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.393
AC:
59803
AN:
152084
Hom.:
14485
Cov.:
32
AF XY:
0.406
AC XY:
30181
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.103
Gnomad4 AMR
AF:
0.505
Gnomad4 ASJ
AF:
0.424
Gnomad4 EAS
AF:
0.704
Gnomad4 SAS
AF:
0.552
Gnomad4 FIN
AF:
0.572
Gnomad4 NFE
AF:
0.480
Gnomad4 OTH
AF:
0.415
Alfa
AF:
0.445
Hom.:
4991
Bravo
AF:
0.374
Asia WGS
AF:
0.554
AC:
1923
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
3.9
DANN
Benign
0.89

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: rs11054731; hg19: chr12-12376465; API