rs142554239
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_001848.3(COL6A1):c.1833C>T(p.Cys611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,608,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
COL6A1
NM_001848.3 synonymous
NM_001848.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.06
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 Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 21-46001263-C-T is Benign according to our data. Variant chr21-46001263-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46001263-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.06 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0016 (244/152358) while in subpopulation AFR AF= 0.00575 (239/41578). AF 95% confidence interval is 0.00515. There are 0 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.1833C>T | p.Cys611= | synonymous_variant | 30/35 | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.1833C>T | p.Cys611= | synonymous_variant | 30/35 | 1 | NM_001848.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00161 AC: 245AN: 152240Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000389 AC: 96AN: 246814Hom.: 0 AF XY: 0.000276 AC XY: 37AN XY: 134032
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GnomAD4 exome AF: 0.000165 AC: 240AN: 1456202Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 104AN XY: 724670
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GnomAD4 genome AF: 0.00160 AC: 244AN: 152358Hom.: 0 Cov.: 34 AF XY: 0.00145 AC XY: 108AN XY: 74504
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 07, 2012 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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