19-47320040-C-A

Variant names:

• chr19-47320040-C-A
• rs201037165
• NM_001736.4:c.263C>A

Variant summary

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

The NM_001736.4(C5AR1):​c.263C>A​(p.Ala88Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A88V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C5AR1 NM_001736.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.263C>A	p.Ala88Glu	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.263C>A	p.Ala88Glu	missense	Exon 2 of 2	ENSP00000347197.2	P21730
	C5AR1	ENST00000594787.1	TSL:5	c.-95C>A		5_prime_UTR	Exon 4 of 4	ENSP00000470613.1	M0QZK7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.011	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.16
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.093	T
Polyphen		0.99	D
Vest4		0.45
MutPred		0.69		Loss of glycosylation at S85 (P = 0.1133)
MVP		0.93
MPC		0.70
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.90
gMVP		0.72
Mutation Taster		=72/28	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: rs201037165; hg19: chr19-47823297;