NM_001736.4:c.682C>G

Variant names:

• chr19-47320459-C-G
• NM_001736.4:c.682C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001736.4(C5AR1):​c.682C>G​(p.Arg228Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: C5AR1 NM_001736.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5AR1	NM_001736.4	c.682C>G	p.Arg228Gly	missense_variant	Exon 2 of 2	ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1	c.784C>G	p.Arg262Gly	missense_variant	Exon 3 of 3		XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000355085.4	c.682C>G	p.Arg228Gly	missense_variant	Exon 2 of 2	1	NM_001736.4	ENSP00000347197.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460624 Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0 AN XY: 726662

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.093
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.71		Loss of MoRF binding (P = 0.0268);
MVP		0.69
MPC		0.72
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.94
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: chr19-47823716;