rs140346737
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001105206.3(LAMA4):c.4436G>A(p.Arg1479His) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1479C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.4436G>A | p.Arg1479His | missense_variant | 32/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.439+5626C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.4436G>A | p.Arg1479His | missense_variant | 32/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251304Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135808
GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727166
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74400
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Arg1472His vari ant in LAMA4 has been identified in 0.1% (4/3736) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS/; dbSNP rs140346737). Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. While this frequency sug gests that this variant is more likely benign, it is too low to confidently rule out a disease causing role. Additional information is needed to fully assess it s clinical significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#44389; Landrum et al., 2016); Reported in an individual with DCM; additional patient-specific details were not reported (Walsh et al., 2017); This variant is associated with the following publications: (PMID: 27532257) - |
LAMA4-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 10, 2022 | 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). - |
Dilated cardiomyopathy 1JJ Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 20, 2021 | 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