NM_001848.3:c.717+33G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001848.3(COL6A1):c.717+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,570,086 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000085 ( 0 hom. )
Consequence
COL6A1
NM_001848.3 intron
NM_001848.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.34
Publications
0 publications found
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]
COL6A1 Gene-Disease associations (from GenCC):
- collagen 6-related myopathyInheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
- Bethlem myopathy 1AInheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
- Ullrich congenital muscular dystrophy 1AInheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- Bethlem myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ullrich congenital muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 21-45987105-G-A is Benign according to our data. Variant chr21-45987105-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 258304.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.717+33G>A | intron_variant | Intron 5 of 34 | ENST00000361866.8 | NP_001839.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152234
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD2 exomes AF: 0.0000111 AC: 2AN: 180972 AF XY: 0.0000103 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
180972
AF XY:
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GnomAD4 exome AF: 0.00000846 AC: 12AN: 1417852Hom.: 0 Cov.: 34 AF XY: 0.00000856 AC XY: 6AN XY: 701164 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1417852
Hom.:
Cov.:
34
AF XY:
AC XY:
6
AN XY:
701164
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32542
American (AMR)
AF:
AC:
1
AN:
38222
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25422
East Asian (EAS)
AF:
AC:
0
AN:
37476
South Asian (SAS)
AF:
AC:
0
AN:
80790
European-Finnish (FIN)
AF:
AC:
0
AN:
48454
Middle Eastern (MID)
AF:
AC:
0
AN:
5712
European-Non Finnish (NFE)
AF:
AC:
11
AN:
1090466
Other (OTH)
AF:
AC:
0
AN:
58768
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
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4
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0.95
Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
152234
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74364
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5204
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68036
Other (OTH)
AF:
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
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0
1
1
2
2
0.00
0.20
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0.60
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0.95
Allele balance
Alfa
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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