rs72986111
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000295550.9(COL6A3):c.6930+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,609,298 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.027 ( 85 hom., cov: 33)
Exomes 𝑓: 0.035 ( 1030 hom. )
Consequence
COL6A3
ENST00000295550.9 intron
ENST00000295550.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.86
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=-0.87).
BP6
Variant 2-237348585-G-A is Benign according to our data. Variant chr2-237348585-G-A is described in ClinVar as [Benign]. Clinvar id is 94973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237348585-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0265 (4039/152246) while in subpopulation SAS AF= 0.0392 (189/4820). AF 95% confidence interval is 0.0348. There are 85 homozygotes in gnomad4. There are 2054 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 85 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.6930+28C>T | intron_variant | ENST00000295550.9 | NP_004360.2 | |||
COL6A3 | NM_057166.5 | c.5109+28C>T | intron_variant | NP_476507.3 | ||||
COL6A3 | NM_057167.4 | c.6312+28C>T | intron_variant | NP_476508.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.6930+28C>T | intron_variant | 1 | NM_004369.4 | ENSP00000295550 | P1 | |||
COL6A3 | ENST00000472056.5 | c.5109+28C>T | intron_variant | 1 | ENSP00000418285 | |||||
COL6A3 | ENST00000353578.9 | c.6312+28C>T | intron_variant | 5 | ENSP00000315873 | |||||
COL6A3 | ENST00000491769.1 | n.1184+28C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0266 AC: 4041AN: 152128Hom.: 85 Cov.: 33
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GnomAD3 exomes AF: 0.0308 AC: 7676AN: 249268Hom.: 161 AF XY: 0.0326 AC XY: 4384AN XY: 134662
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GnomAD4 exome AF: 0.0349 AC: 50898AN: 1457052Hom.: 1030 Cov.: 31 AF XY: 0.0351 AC XY: 25478AN XY: 724930
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GnomAD4 genome AF: 0.0265 AC: 4039AN: 152246Hom.: 85 Cov.: 33 AF XY: 0.0276 AC XY: 2054AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 05, 2012 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at