rs202239067
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004370.6(COL12A1):āc.8565A>Gā(p.Pro2855Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,613,856 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 33)
Exomes š: 0.00028 ( 3 hom. )
Consequence
COL12A1
NM_004370.6 synonymous
NM_004370.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.21
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 6-75097265-T-C is Benign according to our data. Variant chr6-75097265-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 475903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75097265-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.21 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000118 (18/152310) while in subpopulation SAS AF= 0.00332 (16/4824). AF 95% confidence interval is 0.00208. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.8565A>G | p.Pro2855Pro | synonymous_variant | 59/66 | ENST00000322507.13 | NP_004361.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.8565A>G | p.Pro2855Pro | synonymous_variant | 59/66 | 1 | NM_004370.6 | ENSP00000325146.8 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000590 AC: 147AN: 249324Hom.: 0 AF XY: 0.000739 AC XY: 100AN XY: 135282
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GnomAD4 exome AF: 0.000281 AC: 410AN: 1461546Hom.: 3 Cov.: 30 AF XY: 0.000396 AC XY: 288AN XY: 727100
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74466
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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 | Mar 13, 2019 | 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 | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | COL12A1: BP4, BP7 - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 21, 2022 | - - |
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