12-8059976-G-C

Variant names:

• chr12-8059976-G-C
• rs11567805
• NM_004054.4:c.210C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004054.4(C3AR1):​c.210C>G​(p.Leu70Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C3AR1 NM_004054.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

C3AR1 (HGNC:1319): (complement C3a receptor 1) C3a is an anaphylatoxin released during activation of the complement system. The protein encoded by this gene is an orphan G protein-coupled receptor for C3a. Binding of C3a by the encoded receptor activates chemotaxis, granule enzyme release, superoxide anion production, and bacterial opsonization. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3AR1	NM_004054.4	c.210C>G	p.Leu70Leu	synonymous_variant	Exon 2 of 2	ENST00000307637.5	NP_004045.1
C3AR1	NM_001326475.2	c.210C>G	p.Leu70Leu	synonymous_variant	Exon 2 of 2		NP_001313404.1
C3AR1	NM_001326477.2	c.210C>G	p.Leu70Leu	synonymous_variant	Exon 2 of 2		NP_001313406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5	c.210C>G	p.Leu70Leu	synonymous_variant	Exon 2 of 2	1	NM_004054.4	ENSP00000302079.4
C3AR1	ENST00000546241.1	c.210C>G	p.Leu70Leu	synonymous_variant	Exon 2 of 2	4		ENSP00000444500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		1.7

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: rs11567805; hg19: chr12-8212572;