1-207527080-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000651.6(CR1):c.1123A>T(p.Asn375Tyr) 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 0.000024 ( 0 hom., cov: 5)
Exomes 𝑓: 0.000034 ( 2 hom. )
Failed GnomAD Quality Control
Consequence
CR1
NM_000651.6 missense
NM_000651.6 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 0.302
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=0.17302266).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CR1 | NM_000651.6 | c.1123A>T | p.Asn375Tyr | missense_variant | 7/47 | ENST00000367049.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CR1 | ENST00000367049.9 | c.1123A>T | p.Asn375Tyr | missense_variant | 7/47 | 5 | NM_000651.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 40980Hom.: 0 Cov.: 5 FAILED QC
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000653 AC: 3AN: 45956Hom.: 0 AF XY: 0.0000427 AC XY: 1AN XY: 23444
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000336 AC: 24AN: 713296Hom.: 2 Cov.: 9 AF XY: 0.0000279 AC XY: 10AN XY: 358822
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000244 AC: 1AN: 40992Hom.: 0 Cov.: 5 AF XY: 0.0000565 AC XY: 1AN XY: 17702
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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 | Feb 03, 2022 | The c.1123A>T (p.N375Y) alteration is located in exon 7 (coding exon 7) of the CR1 gene. This alteration results from a A to T substitution at nucleotide position 1123, causing the asparagine (N) at amino acid position 375 to be replaced by a tyrosine (Y). 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
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;T
Sift4G
Uncertain
D;D;D;D
Polyphen
0.58
.;.;.;P
Vest4
MutPred
Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP
MPC
2.1
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