1-159713734-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000567.3(CRP):​c.466G>A​(p.Glu156Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CRP
NM_000567.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity CRP_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRPNM_000567.3 linkc.466G>A p.Glu156Lys missense_variant Exon 2 of 2 ENST00000255030.9 NP_000558.2 P02741-1
CRPNM_001329057.2 linkc.466G>A p.Glu156Lys missense_variant Exon 2 of 3 NP_001315986.1 P02741-1
CRPNM_001382703.1 linkc.194-94G>A intron_variant Intron 2 of 2 NP_001369632.1
CRPNM_001329058.2 linkc.198-131G>A intron_variant Intron 2 of 3 NP_001315987.1 P02741-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRPENST00000255030.9 linkc.466G>A p.Glu156Lys missense_variant Exon 2 of 2 1 NM_000567.3 ENSP00000255030.5 P02741-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251468
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.466G>A (p.E156K) alteration is located in exon 2 (coding exon 2) of the CRP gene. This alteration results from a G to A substitution at nucleotide position 466, causing the glutamic acid (E) at amino acid position 156 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.29
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.68
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.27
Sift
Uncertain
0.019
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.24
MutPred
0.85
Gain of ubiquitination at E156 (P = 0.0104);
MVP
0.47
MPC
0.23
ClinPred
0.98
D
GERP RS
3.4
Varity_R
0.82
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748954737; hg19: chr1-159683524; API