rs70940811
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001105206.3(LAMA4):c.3943G>A(p.Val1315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,613,042 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.3943G>A | p.Val1315Ile | missense_variant | 29/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.439+14566C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.3943G>A | p.Val1315Ile | missense_variant | 29/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000782 AC: 119AN: 152078Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00127 AC: 319AN: 250794Hom.: 3 AF XY: 0.00114 AC XY: 154AN XY: 135518
GnomAD4 exome AF: 0.000372 AC: 544AN: 1460846Hom.: 4 Cov.: 31 AF XY: 0.000377 AC XY: 274AN XY: 726752
GnomAD4 genome ? AF: 0.000782 AC: 119AN: 152196Hom.: 1 Cov.: 32 AF XY: 0.000927 AC XY: 69AN XY: 74428
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 05, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Val1308Ile vari ant (LAMA4) has been identified in 2/46 chromosomes from an Asian population, 7/ 2334 chromosomes from the 1000 Genomes population, and 1/3738 chromosomes from a broad but clinically unspecified African American cohort (http://evs.gs.washing ton.edu/EVS, dbSNP rs70940811). Valine (Val) residue at position 1308 is not con served among mammals, suggesting that a change may be tolerated. Computational t ools (PolyPhen2, SIFT, AlignGVGD) also predict this change to be benign although their accuracy is unknown. In summary, this variant is more likely benign but additional information is needed to fully assess its clinical significance. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Dilated cardiomyopathy 1JJ Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 23, 2018 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 21, 2015 | This alteration is classified as 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