rs375770018

Variant names:

• chr19-47341230-C-A
• rs375770018
• NM_001271749.2:c.431C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-47341230-C-A
• chr19-47341230-C-G
• chr19-47341230-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271749.2(C5AR2):​c.431C>A​(p.Thr144Lys) 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. 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. T144M) 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: -0.581
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053052247).

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.431C>A	p.Thr144Lys	missense	Exon 2 of 2	NP_001258678.1	Q9P296
	C5AR2	NM_001271750.2		c.431C>A	p.Thr144Lys	missense	Exon 2 of 2	NP_001258679.1	Q9P296
	C5AR2	NM_018485.3		c.431C>A	p.Thr144Lys	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.431C>A	p.Thr144Lys	missense	Exon 2 of 2	ENSP00000472620.1	Q9P296
	C5AR2	ENST00000600626.1	TSL:1	c.431C>A	p.Thr144Lys	missense	Exon 2 of 2	ENSP00000471184.1	Q9P296
	C5AR2	ENST00000874258.1		c.431C>A	p.Thr144Lys	missense	Exon 3 of 3	ENSP00000544317.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0030
DANN	Benign	0.20
DEOGEN2	Benign	0.091	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.65	N
PhyloP100		-0.58
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.53		Gain of methylation at T144 (P = 0.0326)
MVP		0.061
MPC		0.23
ClinPred		0.11	T
GERP RS		-6.4
Varity_R		0.031
gMVP		0.41
Mutation Taster		=94/6	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: rs375770018; hg19: chr19-47844487;