rs770071302
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_002334.4(LRP4):c.3331G>A(p.Asp1111Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D1111D) has been classified as Likely benign.
Frequency
Consequence
NM_002334.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP4 | NM_002334.4 | c.3331G>A | p.Asp1111Asn | missense_variant | 24/38 | ENST00000378623.6 | |
LRP4 | XM_017017734.2 | c.3331G>A | p.Asp1111Asn | missense_variant | 24/39 | ||
LRP4 | XM_011520103.3 | c.2527G>A | p.Asp843Asn | missense_variant | 18/32 | ||
LRP4 | XM_011520104.3 | c.1096G>A | p.Asp366Asn | missense_variant | 9/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP4 | ENST00000378623.6 | c.3331G>A | p.Asp1111Asn | missense_variant | 24/38 | 1 | NM_002334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251306Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135820
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461824Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2AN XY: 727218
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces aspartic acid with asparagine at codon 1111 of the LRP4 protein (p.Asp1111Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs770071302, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with LRP4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at