rs117330552
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001848.3(COL6A1):c.1823-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,595,018 control chromosomes in the GnomAD database, including 1,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.026 ( 75 hom., cov: 34)
Exomes 𝑓: 0.037 ( 1211 hom. )
Consequence
COL6A1
NM_001848.3 intron
NM_001848.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 21-46001222-C-T is Benign according to our data. Variant chr21-46001222-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46001222-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0262 (3993/152282) while in subpopulation NFE AF= 0.0441 (2996/67974). AF 95% confidence interval is 0.0428. There are 75 homozygotes in gnomad4. There are 1794 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 75 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.1823-31C>T | intron_variant | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.1823-31C>T | intron_variant | 1 | NM_001848.3 | P1 | |||
COL6A1 | ENST00000498614.5 | n.26C>T | non_coding_transcript_exon_variant | 1/6 | 1 | ||||
COL6A1 | ENST00000463060.6 | n.222-31C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0262 AC: 3994AN: 152164Hom.: 75 Cov.: 34
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GnomAD3 exomes AF: 0.0266 AC: 6263AN: 235740Hom.: 134 AF XY: 0.0269 AC XY: 3471AN XY: 128986
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GnomAD4 exome AF: 0.0370 AC: 53417AN: 1442736Hom.: 1211 Cov.: 32 AF XY: 0.0363 AC XY: 26050AN XY: 716954
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GnomAD4 genome ? AF: 0.0262 AC: 3993AN: 152282Hom.: 75 Cov.: 34 AF XY: 0.0241 AC XY: 1794AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
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 05, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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Name
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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