chr12-7089628-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001733.7(C1R):c.530G>A(p.Arg177His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 780,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_001733.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C1R | ENST00000647956.2 | c.530G>A | p.Arg177His | missense_variant | Exon 4 of 11 | NM_001733.7 | ENSP00000497341.1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000133 AC: 33AN: 248534Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134814
GnomAD4 exome AF: 0.000159 AC: 100AN: 628572Hom.: 0 Cov.: 0 AF XY: 0.000158 AC XY: 54AN XY: 342412
GnomAD4 genome AF: 0.000177 AC: 27AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74354
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: C1R c.530G>A (p.Arg177His) results in a non-conservative amino acid change located in the Calcium-binding EGF-like domain (IPR001881) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 248534 control chromosomes, predominantly at a frequency of 0.00021 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 210 fold of the estimated maximal expected allele frequency for a pathogenic variant in C1R causing Ehlers-Danlos syndrome, periodontal type 1 phenotype (1e-06). To our knowledge, no occurrence of c.530G>A in individuals affected with Ehlers-Danlos syndrome, periodontal type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at