Variant rs1417938 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000567.3(CRP):c.61+29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,583,888 control chromosomes in the GnomAD database, including 70,214 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 0.25 ( 5407 hom., cov: 27)

Exomes 𝑓: 0.30 ( 64807 hom. )

Consequence

CRP
NM_000567.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CRP	NM_000567.3 linkuse as main transcript	c.61+29A>T	intron_variant	ENST00000255030.9
CRP	NM_001329057.2 linkuse as main transcript	c.61+29A>T	intron_variant
CRP	NM_001329058.2 linkuse as main transcript	c.61+29A>T	intron_variant
CRP	NM_001382703.1 linkuse as main transcript	c.61+29A>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRP	ENST00000255030.9 linkuse as main transcript	c.61+29A>T		intron_variant		1	NM_000567.3	P1	P02741-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

37363

AN:

147286

Hom.:

5405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.208

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.279

AC:

69472

AN:

249286

Hom.:

10562

AF XY:

0.278

AC XY:

37496

AN XY:

134802

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.368

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.0584

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.296

AC:

425804

AN:

1436510

Hom.:

64807

Cov.:

AF XY:

0.295

AC XY:

210864

AN XY:

715426

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.254

AC:

37388

AN:

147378

Hom.:

5407

Cov.:

AF XY:

0.255

AC XY:

18310

AN XY:

71718

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.278

Hom.:

1231

Bravo

AF:

0.244

Asia WGS

AF:

0.160

AC:

559

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.6

DANN

Benign

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over