rs1205

Variant names:

• chr1-159712443-C-T
• rs1205
• NM_000567.3:c.*1082G>A

Variant summary

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

The NM_000567.3(CRP):​c.*1082G>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 0.31 in 152,742 control chromosomes in the GnomAD database, including 7,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (7891 hom., cov: 32)
  • Exomes 𝑓: 0.34 (50 hom.)
• Consequence: CRP NM_000567.3 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.313
• Publications: 373 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 (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRP	NM_000567.3	c.*1082G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000255030.9	NP_000558.2
CRP	NM_001329057.2	c.*374G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001315986.1
CRP	NM_001382703.1	c.*1082G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001369632.1
CRP	NM_001329058.2	c.*148G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.*1082G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_000567.3	ENSP00000255030.5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47083 AN: 151876 Hom.: 7883 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.345 AC: 257 AN: 746 Hom.: 50 Cov.: 0 AF XY: 0.349 AC XY: 145 AN XY: 416

African (AFR) AF: 0.00 AC: 0 AN: 22

American (AMR) AF: 0.250 AC: 2 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 4 AN: 16

East Asian (EAS) AF: 0.676 AC: 50 AN: 74

South Asian (SAS) AF: 0.375 AC: 3 AN: 8

European-Finnish (FIN) AF: 0.316 AC: 31 AN: 98

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.328 AC: 156 AN: 476

Other (OTH) AF: 0.238 AC: 10 AN: 42

GnomAD4 genome AF: 0.310 AC: 47111 AN: 151996 Hom.: 7891 Cov.: 32 AF XY: 0.314 AC XY: 23355 AN XY: 74292

African (AFR) AF: 0.196 AC: 8117 AN: 41480

American (AMR) AF: 0.373 AC: 5692 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2989 AN: 5154

South Asian (SAS) AF: 0.305 AC: 1467 AN: 4804

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10568

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22682 AN: 67934

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.328 Hom.: 27761

Bravo AF: 0.305

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Inflammation Uncertain:1

-

iDNA Genomics

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.31
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: rs1205; hg19: chr1-159682233;