chr12-8065796-C-T

Variant names:

• chr12-8065796-C-T
• rs7954916
• NM_004054.4:c.-11+482G>A

Variant summary

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

The NM_004054.4(C3AR1):​c.-11+482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 151,528 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000066 (0 hom., cov: 31)
• Consequence: C3AR1 NM_004054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3AR1	NM_004054.4	c.-11+482G>A		intron_variant	Intron 1 of 1	ENST00000307637.5	NP_004045.1
C3AR1	NM_001326475.2	c.-8+482G>A		intron_variant	Intron 1 of 1		NP_001313404.1
C3AR1	NM_001326477.2	c.-11+425G>A		intron_variant	Intron 1 of 1		NP_001313406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5	c.-11+482G>A		intron_variant	Intron 1 of 1	1	NM_004054.4	ENSP00000302079.4
C3AR1	ENST00000546241.1	c.-11+425G>A		intron_variant	Intron 1 of 1	4		ENSP00000444500.1

Frequencies

GnomAD3 genomes AF: 0.0000660 AC: 10 AN: 151528 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.0000294

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000660 AC: 10 AN: 151528 Hom.: 0 Cov.: 31 AF XY: 0.0000947 AC XY: 7 AN XY: 73954

African (AFR) AF: 0.000170 AC: 7 AN: 41196

American (AMR) AF: 0.0000657 AC: 1 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10402

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 6099

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.93
PhyloP100		-0.41

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: rs7954916; hg19: chr12-8218392;