chr19-47320309-C-G

Variant names:

• chr19-47320309-C-G
• rs750580655
• NM_001736.4:c.532C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001736.4(C5AR1):​c.532C>G​(p.Arg178Gly) 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. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R178W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C5AR1 NM_001736.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.44
• Publications: 1 publications found

Genes affected

C5AR1 (HGNC:1338): (complement C5a receptor 1) Enables G protein-coupled receptor activity and complement component C5a receptor activity. Involved in several processes, including complement component C5a signaling pathway; mRNA transcription by RNA polymerase II; and positive regulation of ERK1 and ERK2 cascade. Located in apical part of cell and basolateral plasma membrane. Biomarker of Alzheimer's disease; asthma; chronic obstructive pulmonary disease; rhinitis; and severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07028133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001736.4. 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
	C5AR1	NM_001736.4	MANE Select	c.532C>G	p.Arg178Gly	missense	Exon 2 of 2	NP_001727.2	P21730

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5AR1	ENST00000355085.4	TSL:1 MANE Select	c.532C>G	p.Arg178Gly	missense	Exon 2 of 2	ENSP00000347197.2	P21730
	C5AR1	ENST00000594787.1	TSL:5	c.*123C>G		downstream_gene	N/A	ENSP00000470613.1	M0QZK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.043
DANN	Benign	0.94
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-4.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.063
Sift	Benign	0.19	T
Sift4G	Benign	0.41	T
Polyphen		0.0060	B
Vest4		0.092
MutPred		0.50		Loss of solvent accessibility (P = 0.1077)
MVP		0.18
MPC		0.21
ClinPred		0.058	T
GERP RS		-2.1
Varity_R		0.25
gMVP		0.49
Mutation Taster		=83/17	polymorphism

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: rs750580655; hg19: chr19-47823566;