rs1130864

Variant names:

• chr1-159713301-G-A
• rs1130864
• NM_000567.3:c.*224C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-159713301-G-A
• chr1-159713301-G-C
• chr1-159713301-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000567.3(CRP):​c.*224C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 491,546 control chromosomes in the GnomAD database, including 20,033 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 0.26 (5728 hom., cov: 32)
  • Exomes 𝑓: 0.28 (14305 hom.)
• Consequence: CRP NM_000567.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 281 publications found

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]

ENSG00000297913 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRP	NM_000567.3	c.*224C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000255030.9	NP_000558.2
CRP	NM_001382703.1	c.*224C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001369632.1
CRP	NM_001329057.2	c.*22+202C>T		intron_variant	Intron 2 of 2		NP_001315986.1
CRP	NM_001329058.2	c.*22+202C>T		intron_variant	Intron 3 of 3		NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.*224C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_000567.3	ENSP00000255030.5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39704 AN: 151964 Hom.: 5718 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.279 AC: 94593 AN: 339462 Hom.: 14305 Cov.: 4 AF XY: 0.279 AC XY: 48629 AN XY: 173992

African (AFR) AF: 0.153 AC: 1653 AN: 10774

American (AMR) AF: 0.338 AC: 4028 AN: 11902

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 3220 AN: 11070

East Asian (EAS) AF: 0.0664 AC: 1788 AN: 26912

South Asian (SAS) AF: 0.219 AC: 3686 AN: 16844

European-Finnish (FIN) AF: 0.347 AC: 8005 AN: 23096

Middle Eastern (MID) AF: 0.252 AC: 397 AN: 1574

European-Non Finnish (NFE) AF: 0.305 AC: 66039 AN: 216356

Other (OTH) AF: 0.276 AC: 5777 AN: 20934

GnomAD4 genome AF: 0.261 AC: 39754 AN: 152084 Hom.: 5728 Cov.: 32 AF XY: 0.263 AC XY: 19572 AN XY: 74324

African (AFR) AF: 0.156 AC: 6489 AN: 41498

American (AMR) AF: 0.308 AC: 4702 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3470

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5176

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4826

European-Finnish (FIN) AF: 0.355 AC: 3745 AN: 10544

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21318 AN: 67982

Other (OTH) AF: 0.271 AC: 571 AN: 2108

Alfa AF: 0.296 Hom.: 10895

Bravo AF: 0.255

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.71
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1130864; hg19: chr1-159683091;