chr12-8060196-C-T

Variant names:

• chr12-8060196-C-T
• rs11567804
• NM_004054.4:c.-10-1G>A

Variant summary

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

The NM_004054.4(C3AR1):​c.-10-1G>A variant causes a splice acceptor, intron 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. 3/3 splice prediction tools predicting alterations to normal splicing. 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 splice_acceptor, intron
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646
• Publications: 1 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: 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_004054.4. 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
	C3AR1	NM_004054.4	MANE Select	c.-10-1G>A		splice_acceptor intron	N/A	NP_004045.1	A8K2H7
	C3AR1	NM_001326475.2		c.-7-4G>A		splice_region intron	N/A	NP_001313404.1	A8K2H7
	C3AR1	NM_001326477.2		c.-10-1G>A		splice_acceptor intron	N/A	NP_001313406.1	Q16581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3AR1	ENST00000307637.5	TSL:1 MANE Select	c.-10-1G>A		splice_acceptor intron	N/A	ENSP00000302079.4	Q16581
	C3AR1	ENST00000904894.1		c.-7-4G>A		splice_region intron	N/A	ENSP00000574953.1
	C3AR1	ENST00000904895.1		c.-10-1G>A		splice_acceptor intron	N/A	ENSP00000574954.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	24
DANN	Benign	0.88
PhyloP100		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.80
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -9
DS_AL_spliceai		0.98		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11567804; hg19: chr12-8212792;