rs7579816
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004369.4(COL6A3):c.1313-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,579,334 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 155 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 143 hom. )
Consequence
COL6A3
NM_004369.4 splice_polypyrimidine_tract, intron
NM_004369.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.06
Genes affected
COL6A3 (HGNC:2213): (collagen type VI alpha 3 chain) This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 2-237381516-T-C is Benign according to our data. Variant chr2-237381516-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 94905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237381516-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.1313-17A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000295550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.1313-17A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0241 AC: 3664AN: 152156Hom.: 155 Cov.: 33
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GnomAD3 exomes AF: 0.00645 AC: 1476AN: 228966Hom.: 47 AF XY: 0.00436 AC XY: 547AN XY: 125530
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GnomAD4 exome AF: 0.00284 AC: 4047AN: 1427060Hom.: 143 Cov.: 28 AF XY: 0.00250 AC XY: 1775AN XY: 711248
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GnomAD4 genome ? AF: 0.0242 AC: 3680AN: 152274Hom.: 155 Cov.: 33 AF XY: 0.0234 AC XY: 1740AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 05, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at