chr1-159714051-G-C

Position:

• chr1-159714051-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000567.3(CRP):​c.149C>G​(p.Ala50Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRP NM_000567.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38731176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRP	NM_000567.3	c.149C>G	p.Ala50Gly	missense_variant	2/2	ENST00000255030.9	NP_000558.2
CRP	NM_001329057.2	c.149C>G	p.Ala50Gly	missense_variant	2/3		NP_001315986.1
CRP	NM_001382703.1	c.149C>G	p.Ala50Gly	missense_variant	2/3		NP_001369632.1
CRP	NM_001329058.2	c.149C>G	p.Ala50Gly	missense_variant	2/4		NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.149C>G	p.Ala50Gly	missense_variant	2/2	1	NM_000567.3	ENSP00000255030.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.149C>G (p.A50G) alteration is located in exon 2 (coding exon 2) of the CRP gene. This alteration results from a C to G substitution at nucleotide position 149, causing the alanine (A) at amino acid position 50 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D;.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.1	M;M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.097	T;T;T;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.32	B;P;.;.
Vest4		0.21
MutPred		0.65		Loss of stability (P = 0.063);Loss of stability (P = 0.063);Loss of stability (P = 0.063);Loss of stability (P = 0.063);
MVP		0.80
MPC		0.21
ClinPred		0.80	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159683841;