11-68327273-C-T

Variant summary

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

The NM_002335.4(LRP5):​c.91+14468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,016 control chromosomes in the GnomAD database, including 20,135 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 0.48 ( 20135 hom., cov: 32)

Consequence

LRP5
NM_002335.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.694
Variant links:
Genes affected
LRP5 (HGNC:6697): (LDL receptor related protein 5) This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

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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=-0.92).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRP5NM_002335.4 linkc.91+14468C>T intron_variant ENST00000294304.12 NP_002326.2 O75197

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRP5ENST00000294304.12 linkc.91+14468C>T intron_variant 1 NM_002335.4 ENSP00000294304.6 O75197
LRP5ENST00000529993.5 linkn.91+14468C>T intron_variant 1 ENSP00000436652.1 E9PHY1

Frequencies

GnomAD3 genomes
AF:
0.481
AC:
73052
AN:
151898
Hom.:
20118
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.209
Gnomad AMI
AF:
0.313
Gnomad AMR
AF:
0.611
Gnomad ASJ
AF:
0.603
Gnomad EAS
AF:
0.764
Gnomad SAS
AF:
0.816
Gnomad FIN
AF:
0.661
Gnomad MID
AF:
0.557
Gnomad NFE
AF:
0.539
Gnomad OTH
AF:
0.500
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.481
AC:
73091
AN:
152016
Hom.:
20135
Cov.:
32
AF XY:
0.495
AC XY:
36776
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.612
Gnomad4 ASJ
AF:
0.603
Gnomad4 EAS
AF:
0.765
Gnomad4 SAS
AF:
0.817
Gnomad4 FIN
AF:
0.661
Gnomad4 NFE
AF:
0.539
Gnomad4 OTH
AF:
0.504
Alfa
AF:
0.527
Hom.:
28374
Bravo
AF:
0.460
Asia WGS
AF:
0.735
AC:
2551
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.23
DANN
Benign
0.49

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: rs634008; hg19: chr11-68094741; COSMIC: COSV53713254; API