rs368561027
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_001848.3(COL6A1):c.2614C>T(p.Arg872Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001848.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.2614C>T | p.Arg872Trp | missense_variant | Exon 35 of 35 | ENST00000361866.8 | NP_001839.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152240Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000862 AC: 21AN: 243516Hom.: 0 AF XY: 0.000105 AC XY: 14AN XY: 133222
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1459650Hom.: 0 Cov.: 80 AF XY: 0.0000372 AC XY: 27AN XY: 726108
GnomAD4 genome AF: 0.000203 AC: 31AN: 152358Hom.: 0 Cov.: 35 AF XY: 0.000228 AC XY: 17AN XY: 74500
ClinVar
Submissions by phenotype
not provided Uncertain:3
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The R872W variant in the COL6A1 gene has been reported previously in a patient with Down syndrome and an atrioventricular septal defect; however, additional clinical and family segregation information were not provided (Ackerman et al., 2012). The R872W variant is observed in 19/23246 (0.082%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The R872W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R872W as a variant of uncertain significance. -
Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A Uncertain:1
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Bethlem myopathy 1A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at