12-8058591-T-C

Position:

• chr12-8058591-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307637.5(C3AR1):​c.*146A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 848,390 control chromosomes in the GnomAD database, including 39,505 homozygotes. 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 0.31 (7717 hom., cov: 32)
  • Exomes 𝑓: 0.30 (31788 hom.)
• Consequence: C3AR1 ENST00000307637.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3AR1	NM_004054.4	c.*146A>G		3_prime_UTR_variant	2/2	ENST00000307637.5	NP_004045.1
C3AR1	NM_001326475.2	c.*146A>G		3_prime_UTR_variant	2/2		NP_001313404.1
C3AR1	NM_001326477.2	c.*146A>G		3_prime_UTR_variant	2/2		NP_001313406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5	c.*146A>G		3_prime_UTR_variant	2/2	1	NM_004054.4	ENSP00000302079	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47801 AN: 151918 Hom.: 7706 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.299 AC: 208024 AN: 696354 Hom.: 31788 Cov.: 9 AF XY: 0.300 AC XY: 107668 AN XY: 359346

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.315 AC: 47865 AN: 152036 Hom.: 7717 Cov.: 32 AF XY: 0.313 AC XY: 23299 AN XY: 74326

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.315

Alfa AF: 0.306 Hom.: 14793

Bravo AF: 0.318

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs7842; hg19: chr12-8211187;