19-47341024-C-G

Variant names:

• chr19-47341024-C-G
• NM_001271749.2:c.225C>G
• C5AR2 p.His75Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271749.2(C5AR2):​c.225C>G​(p.His75Gln) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H75Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: C5AR2 NM_001271749.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741
• Publications: 0 publications found

Genes affected

C5AR2 (HGNC:4527): (complement C5a receptor 2) This gene encodes a G-protein coupled receptor 1 family member involved in the complement system of the innate immune response. Unlike classical G-protein coupled receptors, the encoded protein does not associate with intracellular G-proteins. It may instead modulate signal transduction through the beta-arrestin pathway, and may alternatively act as a decoy receptor. This gene may be involved in coronary artery disease and in the pathogenesis of sepsis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26909435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5AR2	NM_001271749.2	MANE Select	c.225C>G	p.His75Gln	missense	Exon 2 of 2	NP_001258678.1	Q9P296
	C5AR2	NM_001271750.2		c.225C>G	p.His75Gln	missense	Exon 2 of 2	NP_001258679.1	Q9P296
	C5AR2	NM_018485.3		c.225C>G	p.His75Gln	missense	Exon 2 of 2	NP_060955.1	Q9P296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5AR2	ENST00000595464.3	TSL:1 MANE Select	c.225C>G	p.His75Gln	missense	Exon 2 of 2	ENSP00000472620.1	Q9P296
	C5AR2	ENST00000600626.1	TSL:1	c.225C>G	p.His75Gln	missense	Exon 2 of 2	ENSP00000471184.1	Q9P296
	C5AR2	ENST00000874258.1		c.225C>G	p.His75Gln	missense	Exon 3 of 3	ENSP00000544317.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.74
PrimateAI	Benign	0.37	T
Sift4G	Uncertain	0.055	T
Varity_R		0.14
gMVP		0.52
Mutation Taster		=45/55	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-47844281;