chr1-207534292-A-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000651.6(CR1):c.1747A>C(p.Thr583Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.19 ( 56 hom., cov: 0)
Exomes 𝑓: 0.025 ( 47 hom. )
Failed GnomAD Quality Control
Consequence
CR1
NM_000651.6 missense
NM_000651.6 missense
Scores
15
Clinical Significance
Conservation
PhyloP100: -2.03
Genes affected
CR1 (HGNC:2334): (complement C3b/C4b receptor 1 (Knops blood group)) This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0077373385).
BP6
?
Variant 1-207534292-A-C is Benign according to our data. Variant chr1-207534292-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2348399.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 8 BG gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CR1 | NM_000651.6 | c.1747A>C | p.Thr583Pro | missense_variant | 11/47 | ENST00000367049.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CR1 | ENST00000367049.9 | c.1747A>C | p.Thr583Pro | missense_variant | 11/47 | 5 | NM_000651.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1151AN: 6128Hom.: 56 Cov.: 0 FAILED QC
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.223 AC: 141AN: 632Hom.: 8 AF XY: 0.188 AC XY: 59AN XY: 314
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0252 AC: 718AN: 28498Hom.: 47 Cov.: 0 AF XY: 0.0227 AC XY: 339AN XY: 14914
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.187 AC: 1152AN: 6168Hom.: 56 Cov.: 0 AF XY: 0.191 AC XY: 540AN XY: 2830
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.45
.;.;.;P
Vest4
MPC
3.4
ClinPred
T
GERP RS
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