rs74852641
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001848.3(COL6A1):c.1773G>A(p.Pro591=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00999 in 1,613,082 control chromosomes in the GnomAD database, including 657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 219 hom., cov: 30)
Exomes 𝑓: 0.0077 ( 438 hom. )
Consequence
COL6A1
NM_001848.3 synonymous
NM_001848.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.662
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 21-45999689-G-A is Benign according to our data. Variant chr21-45999689-G-A is described in ClinVar as [Benign]. Clinvar id is 93828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45999689-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.662 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.1773G>A | p.Pro591= | synonymous_variant | 27/35 | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.1773G>A | p.Pro591= | synonymous_variant | 27/35 | 1 | NM_001848.3 | P1 | |
COL6A1 | ENST00000466285.1 | n.290G>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0323 AC: 4907AN: 151854Hom.: 219 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
4907
AN:
151854
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0167 AC: 4175AN: 249278Hom.: 157 AF XY: 0.0173 AC XY: 2335AN XY: 135112
GnomAD3 exomes
AF:
AC:
4175
AN:
249278
Hom.:
AF XY:
AC XY:
2335
AN XY:
135112
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00767 AC: 11200AN: 1461110Hom.: 438 Cov.: 33 AF XY: 0.00883 AC XY: 6419AN XY: 726840
GnomAD4 exome
AF:
AC:
11200
AN:
1461110
Hom.:
Cov.:
33
AF XY:
AC XY:
6419
AN XY:
726840
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0324 AC: 4919AN: 151972Hom.: 219 Cov.: 30 AF XY: 0.0318 AC XY: 2363AN XY: 74288
GnomAD4 genome
?
AF:
AC:
4919
AN:
151972
Hom.:
Cov.:
30
AF XY:
AC XY:
2363
AN XY:
74288
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
148
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:9
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, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 24, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 25, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 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. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 31, 2017 | - - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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