19-47341101-C-T

Variant names:

• chr19-47341101-C-T
• rs541823800
• NM_001271749.2:c.302C>T

Variant summary

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

The NM_001271749.2(C5AR2):​c.302C>T​(p.Pro101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,604,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P101Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: C5AR2 NM_001271749.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 1 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=0.37878168).

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.302C>T	p.Pro101Leu	missense	Exon 2 of 2	NP_001258678.1	Q9P296
	C5AR2	NM_001271750.2		c.302C>T	p.Pro101Leu	missense	Exon 2 of 2	NP_001258679.1	Q9P296
	C5AR2	NM_018485.3		c.302C>T	p.Pro101Leu	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.302C>T	p.Pro101Leu	missense	Exon 2 of 2	ENSP00000472620.1	Q9P296
	C5AR2	ENST00000600626.1	TSL:1	c.302C>T	p.Pro101Leu	missense	Exon 2 of 2	ENSP00000471184.1	Q9P296
	C5AR2	ENST00000874258.1		c.302C>T	p.Pro101Leu	missense	Exon 3 of 3	ENSP00000544317.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244058 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1452076 Hom.: 0 Cov.: 31 AF XY: 0.00000830 AC XY: 6 AN XY: 722736

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43840

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111874

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.60
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.13	T
Polyphen		0.80	P
Vest4		0.092
MutPred		0.76		Loss of methylation at R96 (P = 0.1242)
MVP		0.51
MPC		0.25
ClinPred		0.41	T
GERP RS		3.2
Varity_R		0.23
gMVP		0.11
Mutation Taster		=77/23	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: rs541823800; hg19: chr19-47844358;