chr6-112133494-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001105206.3(LAMA4):c.3558-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001105206.3 splice_region, splice_polypyrimidine_tract, intron
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.3558-7T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000230538.12 | |||
LOC107986633 | XR_001744299.2 | n.439+17067A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.3558-7T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251036Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135654
GnomAD4 exome AF: 0.0000931 AC: 136AN: 1461292Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 78AN XY: 726968
GnomAD4 genome AF: 0.000131 AC: 20AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74462
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 | Dec 20, 2011 | The 3537-7T>C variant (LAMA4) has not been previously reported not previously id entified by our laboratory. This variant is located in the 3' slice consensus re gion, but does not alter the highly conserved -1 or -2 positions. In addition, t he nucleotides C and T are the two most common nucleotides identified at this po sition, suggesting a change between them may be tolerated. Computational tools d o not predict an impact on splicing, though the accuracy of these tools is unkno wn. Additional information is needed to fully assess the clinical significance o f the 3537-7T>C variant. - |
Dilated cardiomyopathy 1JJ Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2020 | - - |
LAMA4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 20, 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at