1-159713581-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000567.3(CRP):c.619G>C(p.Ala207Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CRP
NM_000567.3 missense
NM_000567.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: -1.08
Genes affected
CRP (HGNC:2367): (C-reactive protein) The protein encoded by this gene belongs to the pentraxin family which also includes serum amyloid P component protein and pentraxin 3. Pentraxins are involved in complement activation and amplification via communication with complement initiation pattern recognition molecules, but also complement regulation via recruitment of complement regulators. The encoded protein has a calcium dependent ligand binding domain with a distinctive flattened beta-jellyroll structure. It exists in two forms as either a pentamer in circulation or as a nonsoluble monomer in tissues. It is involved in several host defense related functions based on its ability to recognize foreign pathogens and damaged cells of the host and to initiate their elimination by interacting with humoral and cellular effector systems in the blood. Consequently, the level of this protein in plasma increases greatly during acute phase response to tissue injury, infection, or other inflammatory stimuli. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRP | NM_000567.3 | c.619G>C | p.Ala207Pro | missense_variant | 2/2 | ENST00000255030.9 | |
CRP | NM_001329057.2 | c.619G>C | p.Ala207Pro | missense_variant | 2/3 | ||
CRP | NM_001382703.1 | c.253G>C | p.Ala85Pro | missense_variant | 3/3 | ||
CRP | NM_001329058.2 | c.220G>C | p.Ala74Pro | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRP | ENST00000255030.9 | c.619G>C | p.Ala207Pro | missense_variant | 2/2 | 1 | NM_000567.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251282Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135844
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727208
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN 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 | Apr 27, 2022 | The c.619G>C (p.A207P) alteration is located in exon 2 (coding exon 2) of the CRP gene. This alteration results from a G to C substitution at nucleotide position 619, causing the alanine (A) at amino acid position 207 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;.;.
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;T;T
Sift4G
Uncertain
D;T;T;T;T
Polyphen
D;.;P;.;.
Vest4
MutPred
Loss of sheet (P = 0.0817);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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