chr1-159713309-G-A

Variant names:

• chr1-159713309-G-A
• rs3093066
• NM_000567.3:c.*216C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000567.3(CRP):​c.*216C>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 0.00000268 in 372,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>T		3_prime_UTR	Exon 2 of 2	NP_000558.2
	CRP	NM_001382703.1		c.*216C>T		3_prime_UTR	Exon 3 of 3	NP_001369632.1
	CRP	NM_001329057.2		c.*22+194C>T		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>T		3_prime_UTR	Exon 2 of 2	ENSP00000255030.5
	CRP	ENST00000437342.1	TSL:1	c.*22+194C>T		intron	N/A	ENSP00000402788.1
	CRP	ENST00000368110.1	TSL:3	c.*22+194C>T		intron	N/A	ENSP00000357091.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000268 AC: 1 AN: 372678 Hom.: 0 Cov.: 5 AF XY: 0.00000523 AC XY: 1 AN XY: 191228

African (AFR) AF: 0.00 AC: 0 AN: 11360

American (AMR) AF: 0.00 AC: 0 AN: 12908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11770

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 21434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1690

European-Non Finnish (NFE) AF: 0.00000420 AC: 1 AN: 237970

Other (OTH) AF: 0.00 AC: 0 AN: 22536

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 179

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.55
DANN	Benign	0.44
PhyloP100		-0.54

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;