rs1417938

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

2

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]

Genome browser will be placed here

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 HGVSp Effect #exon/exons MANE UniProt
CRPNM_000567.3 linkuse as main transcriptc.61+29A>T intron_variant ENST00000255030.9
CRPNM_001329057.2 linkuse as main transcriptc.61+29A>T intron_variant
CRPNM_001329058.2 linkuse as main transcriptc.61+29A>T intron_variant
CRPNM_001382703.1 linkuse as main transcriptc.61+29A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRPENST00000255030.9 linkuse as main transcriptc.61+29A>T intron_variant 1 NM_000567.3 P1P02741-1

Frequencies

GnomAD3 genomes
AF:
0.254
AC:
37363
AN:
147286
Hom.:
5405
Cov.:
27
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.:
30
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.:
27
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.

Other links and lift over

dbSNP: rs1417938; hg19: chr1-159684186; COSMIC: COSV54812545; COSMIC: COSV54812545; API