rs371949188
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_004370.6(COL12A1):c.8421C>T(p.Arg2807Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,614,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00090 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
COL12A1
NM_004370.6 synonymous
NM_004370.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
COL12A1 (HGNC:2188): (collagen type XII alpha 1 chain) This gene encodes the alpha chain of type XII collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XII collagen is a homotrimer found in association with type I collagen, an association that is thought to modify the interactions between collagen I fibrils and the surrounding matrix. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 6-75102047-G-A is Benign according to our data. Variant chr6-75102047-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0009 (137/152256) while in subpopulation AFR AF= 0.00315 (131/41538). AF 95% confidence interval is 0.00271. There are 1 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.8421C>T | p.Arg2807Arg | synonymous_variant | 57/66 | ENST00000322507.13 | NP_004361.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.8421C>T | p.Arg2807Arg | synonymous_variant | 57/66 | 1 | NM_004370.6 | ENSP00000325146.8 |
Frequencies
GnomAD3 genomes AF: 0.000900 AC: 137AN: 152138Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000205 AC: 51AN: 249328Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135262
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GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727194
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GnomAD4 genome AF: 0.000900 AC: 137AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000927 AC XY: 69AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
COL12A1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 08, 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2019 | - - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at