rs1556425727
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PVS1_ModeratePP3BP6_Very_Strong
The NM_001848.3(COL6A1):c.1002+6_1002+88del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,294,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00013 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
COL6A1
NM_001848.3 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_001848.3 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.34
Genes affected
COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.01425332 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
?
Variant 21-45990407-GGTGGACGGCGTGAAGGTGACTGGGGGGAGATAGGATGGACGGGGAGGGACGAGGAGGAATGGGGCGAGATGGGGAGGGACGGA-G is Benign according to our data. Variant chr21-45990407-GGTGGACGGCGTGAAGGTGACTGGGGGGAGATAGGATGGACGGGGAGGGACGAGGAGGAATGGGGCGAGATGGGGAGGGACGGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 543025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45990407-GGTGGACGGCGTGAAGGTGACTGGGGGGAGATAGGATGGACGGGGAGGGACGAGGAGGAATGGGGCGAGATGGGGAGGGACGGA-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.1002+6_1002+88del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 13/35 | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.1002+6_1002+88del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 13/35 | 1 | NM_001848.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 173AN: 48458Hom.: 0 Cov.: 0 FAILED QC
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GnomAD4 exome AF: 0.000132 AC: 171AN: 1294916Hom.: 0 AF XY: 0.000121 AC XY: 78AN XY: 643186
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00357 AC: 173AN: 48508Hom.: 0 Cov.: 0 AF XY: 0.00382 AC XY: 89AN XY: 23292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
COL6A1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 27, 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). - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Likely benign and reported on 03-09-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at