Variant 1-159713648-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000567.3(CRP):c.552G>C(p.Leu184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,614,146 control chromosomes in the GnomAD database, including 2,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.045 ( 225 hom., cov: 31)

Exomes 𝑓: 0.058 ( 2694 hom. )

Consequence

CRP
NM_000567.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRP	NM_000567.3 linkuse as main transcript	c.552G>C	p.Leu184=	synonymous_variant	2/2	ENST00000255030.9
CRP	NM_001329057.2 linkuse as main transcript	c.552G>C	p.Leu184=	synonymous_variant	2/3
CRP	NM_001329058.2 linkuse as main transcript	c.198-45G>C		intron_variant
CRP	NM_001382703.1 linkuse as main transcript	c.194-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRP	ENST00000255030.9 linkuse as main transcript	c.552G>C	p.Leu184=	synonymous_variant	2/2	1	NM_000567.3	P1	P02741-1

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6839

AN:

152148

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00997

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.0671

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0569

GnomAD3 exomes

AF:

0.0509

AC:

12798

AN:

251474

Hom.:

431

AF XY:

0.0512

AC XY:

6957

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0827

Gnomad EAS exome

AF:

0.0788

Gnomad SAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0564

GnomAD4 exome

AF:

0.0577

AC:

84405

AN:

1461880

Hom.:

2694

Cov.:

AF XY:

0.0572

AC XY:

41575

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00893

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.0805

Gnomad4 EAS exome

AF:

0.0504

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.0601

Gnomad4 NFE exome

AF:

0.0633

Gnomad4 OTH exome

AF:

0.0558

GnomAD4 genome

AF:

0.0449

AC:

6832

AN:

152266

Hom.:

225

Cov.:

AF XY:

0.0433

AC XY:

3223

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.0390

Gnomad4 ASJ

AF:

0.0832

Gnomad4 EAS

AF:

0.0665

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0566

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0523

Hom.:

Bravo

AF:

0.0423

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.0601

EpiControl

AF:

0.0607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.5

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over