NM_001733.7:c.890G>A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_001733.7(C1R):c.890G>A(p.Gly297Asp) 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 Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 31)
Consequence
C1R
NM_001733.7 missense
NM_001733.7 missense
Scores
10
4
2
Clinical Significance
Conservation
PhyloP100: 6.97
Publications
1 publications found
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]
C1R Gene-Disease associations (from GenCC):
- Ehlers-Danlos syndrome, periodontal type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
- autosomal systemic lupus erythematosus type 16Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ehlers-Danlos syndrome, periodontitis typeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 16 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 1 uncertain in NM_001733.7
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
Variant 12-7088865-C-T is Pathogenic according to our data. Variant chr12-7088865-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 372129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001733.7. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| C1R | MANE Select | c.890G>A | p.Gly297Asp | missense | Exon 6 of 11 | ENSP00000497341.1 | A0A3B3ISR2 | ||
| C1R | c.1043G>A | p.Gly348Asp | missense | Exon 7 of 12 | ENSP00000573910.1 | ||||
| C1R | c.962G>A | p.Gly321Asp | missense | Exon 7 of 12 | ENSP00000573909.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Ehlers-Danlos syndrome, periodontal type 1 (2)
1
-
-
Ehlers-Danlos syndrome, periodontal type 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K299 (P = 0.0526)
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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