rs148865136
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_002334.4(LRP4):āc.5182A>Gā(p.Ile1728Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,613,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_002334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP4 | NM_002334.4 | c.5182A>G | p.Ile1728Val | missense_variant | 36/38 | ENST00000378623.6 | |
LRP4-AS1 | NR_038909.1 | n.198-8565T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP4 | ENST00000378623.6 | c.5182A>G | p.Ile1728Val | missense_variant | 36/38 | 1 | NM_002334.4 | P1 | |
LRP4-AS1 | ENST00000502049.3 | n.193-8565T>C | intron_variant, non_coding_transcript_variant | 2 | |||||
LRP4-AS1 | ENST00000531719.5 | n.292-8565T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000447 AC: 68AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000371 AC: 93AN: 250946Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135608
GnomAD4 exome AF: 0.000436 AC: 637AN: 1461242Hom.: 0 Cov.: 30 AF XY: 0.000446 AC XY: 324AN XY: 727014
GnomAD4 genome ? AF: 0.000447 AC: 68AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74454
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2022 | The c.5182A>G (p.I1728V) alteration is located in exon 36 (coding exon 36) of the LRP4 gene. This alteration results from a A to G substitution at nucleotide position 5182, causing the isoleucine (I) at amino acid position 1728 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Cenani-Lenz syndactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1728 of the LRP4 protein (p.Ile1728Val). This variant is present in population databases (rs148865136, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with LRP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 288220). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRP4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 22, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at