rs145897390
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001105206.3(LAMA4):c.5344C>T(p.Arg1782Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,614,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.5344C>T | p.Arg1782Cys | missense_variant | 39/39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.5344C>T | p.Arg1782Cys | missense_variant | 39/39 | 1 | NM_001105206.3 | ENSP00000230538.7 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000171 AC: 43AN: 251280Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135796
GnomAD4 exome AF: 0.000133 AC: 194AN: 1461774Hom.: 1 Cov.: 31 AF XY: 0.000140 AC XY: 102AN XY: 727178
GnomAD4 genome AF: 0.000440 AC: 67AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74466
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg1775Cys va riant LAMA4 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.13% (6/4400) of African American chromosomes by th e NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs145 897390). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the c linical significance of the p.Arg1775Cys variant is uncertain, its frequency sug gests that it is more likely to be benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2023 | - - |
Dilated cardiomyopathy 1JJ Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 09, 2023 | - - |
LAMA4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 23, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at