rs16886258
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004370.6(COL12A1):c.834T>G(p.Ala278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,612,462 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 41 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 49 hom. )
Consequence
COL12A1
NM_004370.6 synonymous
NM_004370.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.695
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=-0.53).
BP6
?
Variant 6-75188525-A-C is Benign according to our data. Variant chr6-75188525-A-C is described in ClinVar as [Benign]. Clinvar id is 259352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75188525-A-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.695 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2028/152242) while in subpopulation AFR AF= 0.0465 (1934/41556). AF 95% confidence interval is 0.0448. There are 41 homozygotes in gnomad4. There are 973 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 41 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.834T>G | p.Ala278= | synonymous_variant | 8/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.834T>G | p.Ala278= | synonymous_variant | 8/66 | 1 | NM_004370.6 | P4 | |
COL12A1 | ENST00000345356.10 | c.73+14195T>G | intron_variant | 1 | |||||
COL12A1 | ENST00000483888.6 | c.834T>G | p.Ala278= | synonymous_variant | 8/65 | 5 | A1 | ||
COL12A1 | ENST00000416123.6 | c.834T>G | p.Ala278= | synonymous_variant | 7/63 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0133 AC: 2022AN: 152124Hom.: 41 Cov.: 33
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GnomAD3 exomes AF: 0.00355 AC: 879AN: 247726Hom.: 24 AF XY: 0.00271 AC XY: 364AN XY: 134434
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GnomAD4 exome AF: 0.00141 AC: 2055AN: 1460220Hom.: 49 Cov.: 31 AF XY: 0.00117 AC XY: 849AN XY: 726430
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GnomAD4 genome ? AF: 0.0133 AC: 2028AN: 152242Hom.: 41 Cov.: 33 AF XY: 0.0131 AC XY: 973AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | - - |
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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