3-112929058-G-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_138806.4(CD200R1):c.527C>A(p.Pro176His) variant causes a missense change. The variant allele was found at a frequency of 0.0000632 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000059 ( 0 hom. )
Consequence
CD200R1
NM_138806.4 missense
NM_138806.4 missense
Scores
5
9
3
Clinical Significance
Conservation
PhyloP100: 4.85
Genes affected
CD200R1 (HGNC:24235): (CD200 receptor 1) This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.943
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CD200R1 | NM_138806.4 | c.527C>A | p.Pro176His | missense_variant | 5/8 | ENST00000308611.8 | NP_620161.1 | |
CD200R1 | NM_170780.3 | c.458C>A | p.Pro153His | missense_variant | 4/7 | NP_740750.1 | ||
CD200R1 | NM_138939.3 | c.*85C>A | 3_prime_UTR_variant | 4/4 | NP_620385.1 | |||
CD200R1 | NM_138940.3 | c.*85C>A | 3_prime_UTR_variant | 3/3 | NP_620386.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CD200R1 | ENST00000308611.8 | c.527C>A | p.Pro176His | missense_variant | 5/8 | 1 | NM_138806.4 | ENSP00000311035.3 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250642Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135492
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GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461514Hom.: 0 Cov.: 56 AF XY: 0.0000564 AC XY: 41AN XY: 727058
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74338
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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 | Oct 12, 2024 | The c.527C>A (p.P176H) alteration is located in exon 5 (coding exon 5) of the CD200R1 gene. This alteration results from a C to A substitution at nucleotide position 527, causing the proline (P) at amino acid position 176 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Vest4
MVP
MPC
0.98
ClinPred
D
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