chr1-159713309-G-T

Variant names:

• chr1-159713309-G-T
• rs3093066
• NM_000567.3:c.*216C>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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 18 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000567.3. 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.*216C>A		3_prime_UTR	Exon 2 of 2	NP_000558.2
	CRP	NM_001382703.1		c.*216C>A		3_prime_UTR	Exon 3 of 3	NP_001369632.1
	CRP	NM_001329057.2		c.*22+194C>A		intron	N/A	NP_001315986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRP	ENST00000255030.9	TSL:1 MANE Select	c.*216C>A		3_prime_UTR	Exon 2 of 2	ENSP00000255030.5
	CRP	ENST00000437342.1	TSL:1	c.*22+194C>A		intron	N/A	ENSP00000402788.1
	CRP	ENST00000368110.1	TSL:3	c.*22+194C>A		intron	N/A	ENSP00000357091.1

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9989 AN: 152056 Hom.: 1089 Cov.: 31

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.: 5 AF XY: 0.00844 AC XY: 1614 AN XY: 191218

African (AFR) AF: 0.224 AC: 2537 AN: 11346

American (AMR) AF: 0.0162 AC: 209 AN: 12908

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 44 AN: 11770

East Asian (EAS) AF: 0.00 AC: 0 AN: 28096

South Asian (SAS) AF: 0.00159 AC: 34 AN: 21434

European-Finnish (FIN) AF: 0.0000401 AC: 1 AN: 24914

Middle Eastern (MID) AF: 0.0456 AC: 77 AN: 1690

European-Non Finnish (NFE) AF: 0.00106 AC: 253 AN: 237970

Other (OTH) AF: 0.0221 AC: 499 AN: 22538

GnomAD4 genome AF: 0.0659 AC: 10029 AN: 152174 Hom.: 1099 Cov.: 31 AF XY: 0.0639 AC XY: 4757 AN XY: 74394

African (AFR) AF: 0.228 AC: 9442 AN: 41456

American (AMR) AF: 0.0232 AC: 355 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68016

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0207 Hom.: 179

Bravo AF: 0.0748

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-0.54
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: rs3093066; hg19: chr1-159683099;