rs563043611
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001848.3(COL6A1):c.2746G>A(p.Val916Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,090 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
COL6A1
NM_001848.3 missense
NM_001848.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 2.59
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 Likely_benign. Variant got -3 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2020135).
BP6
?
Variant 21-46003672-G-A is Benign according to our data. Variant chr21-46003672-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 420901.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=4, Benign=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.2746G>A | p.Val916Ile | missense_variant | 35/35 | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.2746G>A | p.Val916Ile | missense_variant | 35/35 | 1 | NM_001848.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152254Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000683 AC: 17AN: 249044Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135262
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460718Hom.: 0 Cov.: 46 AF XY: 0.0000151 AC XY: 11AN XY: 726678
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 05, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 20, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
COL6A1-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2023 | The COL6A1 c.2746G>A variant is predicted to result in the amino acid substitution p.Val916Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.042% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-47423586-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of loop (P = 0.2237);.;
MVP
MPC
ClinPred
T
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Varity_R
gMVP
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