1-159713648-C-G

Variant names:

• chr1-159713648-C-G
• rs1800947
• NM_000567.3:c.552G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001382703.1(CRP):​c.194-8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,614,146 control chromosomes in the GnomAD database, including 2,919 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (225 hom., cov: 31)
  • Exomes 𝑓: 0.058 (2694 hom.)
• Consequence: CRP NM_001382703.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 293 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382703.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRP	NM_000567.3	MANE Select	c.552G>C	p.Leu184Leu	synonymous	Exon 2 of 2	NP_000558.2
	CRP	NM_001329057.2		c.552G>C	p.Leu184Leu	synonymous	Exon 2 of 3	NP_001315986.1
	CRP	NM_001382703.1		c.194-8G>C		splice_region intron	N/A	NP_001369632.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRP	ENST00000255030.9	TSL:1 MANE Select	c.552G>C	p.Leu184Leu	synonymous	Exon 2 of 2	ENSP00000255030.5
	CRP	ENST00000437342.1	TSL:1	c.18G>C	p.Leu6Leu	synonymous	Exon 2 of 3	ENSP00000402788.1
	CRP	ENST00000368110.1	TSL:3	c.194-8G>C		splice_region intron	N/A	ENSP00000357091.1

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6839 AN: 152148 Hom.: 225 Cov.: 31

Gnomad AFR AF: 0.00997

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0569

GnomAD2 exomes AF: 0.0509 AC: 12798 AN: 251474 AF XY: 0.0512

Gnomad AFR exome AF: 0.00997

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0827

Gnomad EAS exome AF: 0.0788

Gnomad FIN exome AF: 0.0578

Gnomad NFE exome AF: 0.0647

Gnomad OTH exome AF: 0.0564

GnomAD4 exome AF: 0.0577 AC: 84405 AN: 1461880 Hom.: 2694 Cov.: 31 AF XY: 0.0572 AC XY: 41575 AN XY: 727242

African (AFR) AF: 0.00893 AC: 299 AN: 33480

American (AMR) AF: 0.0227 AC: 1016 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 2104 AN: 26136

East Asian (EAS) AF: 0.0504 AC: 2002 AN: 39700

South Asian (SAS) AF: 0.0214 AC: 1850 AN: 86258

European-Finnish (FIN) AF: 0.0601 AC: 3213 AN: 53418

Middle Eastern (MID) AF: 0.0270 AC: 156 AN: 5768

European-Non Finnish (NFE) AF: 0.0633 AC: 70394 AN: 1112002

Other (OTH) AF: 0.0558 AC: 3371 AN: 60396

GnomAD4 genome AF: 0.0449 AC: 6832 AN: 152266 Hom.: 225 Cov.: 31 AF XY: 0.0433 AC XY: 3223 AN XY: 74448

African (AFR) AF: 0.00994 AC: 413 AN: 41554

American (AMR) AF: 0.0390 AC: 597 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.0665 AC: 344 AN: 5176

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4824

European-Finnish (FIN) AF: 0.0566 AC: 600 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4297 AN: 68016

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0523 Hom.: 97

Bravo AF: 0.0423

Asia WGS AF: 0.0400 AC: 140 AN: 3478

EpiCase AF: 0.0601

EpiControl AF: 0.0607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.5
DANN	Benign	0.88
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1800947; hg19: chr1-159683438; COSMIC: COSV99660461;