rs187358458
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_004370.6(COL12A1):c.3835+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000582 in 1,613,816 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).
Frequency
Consequence
NM_004370.6 splice_donor_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.3835+4A>G | splice_donor_region_variant, intron_variant | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.3835+4A>G | splice_donor_region_variant, intron_variant | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000493 AC: 75AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000285 AC: 71AN: 248854Hom.: 0 AF XY: 0.000274 AC XY: 37AN XY: 134978
GnomAD4 exome AF: 0.000592 AC: 865AN: 1461558Hom.: 0 Cov.: 31 AF XY: 0.000572 AC XY: 416AN XY: 727088
GnomAD4 genome AF: 0.000493 AC: 75AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74442
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 14, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 19, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2020 | - - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | This sequence change falls in intron 19 of the COL12A1 gene. It does not directly change the encoded amino acid sequence of the COL12A1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs187358458, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575462). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at