rs116776267

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_000567.3(CRP):c.134C>T(p.Thr45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,613,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

CRP
NM_000567.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.267

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]

CRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010433525).

BP6

Variant 1-159714066-G-A is Benign according to our data. Variant chr1-159714066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3356915.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRP	NM_000567.3 link	c.134C>T	p.Thr45Met	missense_variant	Exon 2 of 2	ENST00000255030.9	NP_000558.2	P02741-1
CRP	NM_001329057.2 link	c.134C>T	p.Thr45Met	missense_variant	Exon 2 of 3		NP_001315986.1	P02741-1
CRP	NM_001382703.1 link	c.134C>T	p.Thr45Met	missense_variant	Exon 2 of 3		NP_001369632.1
CRP	NM_001329058.2 link	c.134C>T	p.Thr45Met	missense_variant	Exon 2 of 4		NP_001315987.1	P02741-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9 link	c.134C>T	p.Thr45Met	missense_variant	Exon 2 of 2	1	NM_000567.3	ENSP00000255030.5		P02741-1

Frequencies

GnomAD3 genomes

AF:

0.000704

AC:

107

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000224

AC:

AN:

249882

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.00204

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461330

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000757

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000703

AC:

107

AN:

152110

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000756

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CRP-related disorder

Benign:1

Aug 20, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;.;T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.67

T;T;.;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Benign

0.081

T;D;D;D

Polyphen

0.83

P;D;.;.

Vest4

0.11

MVP

0.28

MPC

0.10

ClinPred

0.021

GERP RS

-0.19

Varity_R

0.11

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over