Variant chr1-159713309-G-T 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.*216C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 524,840 control chromosomes in the GnomAD database, including 1,406 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 0.066 ( 1099 hom., cov: 31)

Exomes 𝑓: 0.0098 ( 307 hom. )

Consequence

CRP
NM_000567.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CRP	NM_000567.3 linkuse as main transcript	c.*216C>A	3_prime_UTR_variant	2/2	ENST00000255030.9	NP_000558.2
CRP	NM_001382703.1 linkuse as main transcript	c.*216C>A	3_prime_UTR_variant	3/3		NP_001369632.1
CRP	NM_001329057.2 linkuse as main transcript	c.*22+194C>A	intron_variant			NP_001315986.1
CRP	NM_001329058.2 linkuse as main transcript	c.*22+194C>A	intron_variant			NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9 linkuse as main transcript	c.*216C>A		3_prime_UTR_variant	2/2	1	NM_000567.3	ENSP00000255030	P1	P02741-1

Frequencies

GnomAD3 genomes

AF:

0.0657

AC:

9989

AN:

152056

Hom.:

1089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0459

GnomAD4 exome

AF:

0.00981

AC:

3654

AN:

372666

Hom.:

307

Cov.:

AF XY:

0.00844

AC XY:

1614

AN XY:

191218

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.00374

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.0000401

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.0221

GnomAD4 genome

AF:

0.0659

AC:

10029

AN:

152174

Hom.:

1099

Cov.:

AF XY:

0.0639

AC XY:

4757

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0748

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.44

DANN

Benign

0.43

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