rs782805733
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001105206.3(LAMA4):c.4583G>T(p.Arg1528Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1528C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105206.3 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 |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.4583G>T | p.Arg1528Leu | missense_variant | 33/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.439+3938C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.4583G>T | p.Arg1528Leu | missense_variant | 33/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152118Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250836Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135552
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461566Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727102
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152118Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74300
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | LAMA4 NM_002290.4 exon 33 p.Arg1521Leu (c.4562G>A): This variant has not been reported in the literature and is present in 0.01% (3/24968) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-112441568-C-A). This variant is present in ClinVar (Variation ID:406147). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 406147). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs782805733, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1521 of the LAMA4 protein (p.Arg1521Leu). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 10, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Feb 17, 2022 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2022 | The p.R1521L variant (also known as c.4562G>T), located in coding exon 32 of the LAMA4 gene, results from a G to T substitution at nucleotide position 4562. The arginine at codon 1521 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at