chr1-207542212-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000651.6(CR1):c.1868C>T(p.Ala623Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00035 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CR1
NM_000651.6 missense
NM_000651.6 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 0.230
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 Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19929105).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CR1 | NM_000651.6 | c.1868C>T | p.Ala623Val | missense_variant | 13/47 | ENST00000367049.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CR1 | ENST00000367049.9 | c.1868C>T | p.Ala623Val | missense_variant | 13/47 | 5 | NM_000651.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 8Hom.: 0 Cov.: 0 FAILED QC
GnomAD3 genomes
?
AF:
AC:
0
AN:
8
Hom.:
Cov.:
0
FAILED QC
Gnomad AFR
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000350 AC: 39AN: 111438Hom.: 0 Cov.: 0 AF XY: 0.000360 AC XY: 21AN XY: 58268
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
39
AN:
111438
Hom.:
Cov.:
0
AF XY:
AC XY:
21
AN XY:
58268
Gnomad4 AFR exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 8Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
GnomAD4 genome
?
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
8
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0
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0
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2
Gnomad4 AFR
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2022 | The c.1868C>T (p.A623V) alteration is located in exon 13 (coding exon 13) of the CR1 gene. This alteration results from a C to T substitution at nucleotide position 1868, causing the alanine (A) at amino acid position 623 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.94
.;.;.;P
Vest4
MutPred
Loss of glycosylation at T621 (P = 0.184);.;Loss of glycosylation at T621 (P = 0.184);Loss of glycosylation at T621 (P = 0.184);
MVP
MPC
2.9
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at