rs117936904
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_002334.4(LRP4):c.5165T>A(p.Leu1722His) variant causes a missense change. The variant allele was found at a frequency of 0.0206 in 1,611,148 control chromosomes in the GnomAD database, including 438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 50 hom., cov: 32)
Exomes 𝑓: 0.021 ( 388 hom. )
Consequence
LRP4
NM_002334.4 missense
NM_002334.4 missense
Scores
1
9
8
Clinical Significance
Conservation
PhyloP100: 6.74
Genes affected
LRP4 (HGNC:6696): (LDL receptor related protein 4) This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, LRP4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007769525).
BP6
?
Variant 11-46864526-A-T is Benign according to our data. Variant chr11-46864526-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 304849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-46864526-A-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0178 (2711/152350) while in subpopulation NFE AF= 0.0228 (1552/68036). AF 95% confidence interval is 0.0219. There are 50 homozygotes in gnomad4. There are 1366 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 50 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP4 | NM_002334.4 | c.5165T>A | p.Leu1722His | missense_variant | 36/38 | ENST00000378623.6 | |
LRP4-AS1 | NR_038909.1 | n.198-8548A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP4 | ENST00000378623.6 | c.5165T>A | p.Leu1722His | missense_variant | 36/38 | 1 | NM_002334.4 | P1 | |
LRP4-AS1 | ENST00000502049.3 | n.193-8548A>T | intron_variant, non_coding_transcript_variant | 2 | |||||
LRP4-AS1 | ENST00000531719.5 | n.292-8548A>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0178 AC: 2713AN: 152232Hom.: 50 Cov.: 32
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GnomAD3 exomes AF: 0.0194 AC: 4875AN: 250854Hom.: 77 AF XY: 0.0196 AC XY: 2656AN XY: 135570
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GnomAD4 exome AF: 0.0209 AC: 30531AN: 1458798Hom.: 388 Cov.: 29 AF XY: 0.0204 AC XY: 14826AN XY: 726026
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GnomAD4 genome ? AF: 0.0178 AC: 2711AN: 152350Hom.: 50 Cov.: 32 AF XY: 0.0183 AC XY: 1366AN XY: 74492
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ESP6500AA
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ExAC
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2257
Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Cenani-Lenz syndactyly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at