rs1057518643
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001733.7(C1R):c.869A>G(p.Asp290Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
C1R
NM_001733.7 missense
NM_001733.7 missense
Scores
5
5
2
Clinical Significance
Conservation
PhyloP100: 7.07
Genes affected
C1R (HGNC:1246): (complement C1r) This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a domain CUB 2 (size 112) in uniprot entity C1R_HUMAN there are 13 pathogenic changes around while only 5 benign (72%) in NM_001733.7
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.985
PP5
?
Variant 12-7088886-T-C is Pathogenic according to our data. Variant chr12-7088886-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 267356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-7088886-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1R | NM_001733.7 | c.869A>G | p.Asp290Gly | missense_variant | 6/11 | ENST00000647956.2 | |
C1R | NM_001354346.2 | c.911A>G | p.Asp304Gly | missense_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1R | ENST00000647956.2 | c.869A>G | p.Asp290Gly | missense_variant | 6/11 | NM_001733.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, periodontal type 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 31, 2016 | - - |
Pathogenic, criteria provided, single submitter | research | Institute of Human Genetics, Medical University Innsbruck | Aug 23, 2016 | - - |
Ehlers-Danlos syndrome, periodontal type 2 Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Oct 13, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.96, 0.44
.;.;D;B
Vest4
0.91, 0.91, 0.92
MutPred
Gain of catalytic residue at D290 (P = 0.1414);Gain of catalytic residue at D290 (P = 0.1414);.;.;
MVP
0.53
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at