chr12-8058591-T-C

Variant names:

• chr12-8058591-T-C
• rs7842
• NM_004054.4:c.*146A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004054.4(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 NM_004054.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 21 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: Benign. The variant received -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.

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.*146A>G		3_prime_UTR	Exon 2 of 2	NP_004045.1	A8K2H7
	C3AR1	NM_001326475.2		c.*146A>G		3_prime_UTR	Exon 2 of 2	NP_001313404.1	A8K2H7
	C3AR1	NM_001326477.2		c.*146A>G		3_prime_UTR	Exon 2 of 2	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.*146A>G		3_prime_UTR	Exon 2 of 2	ENSP00000302079.4	Q16581
	C3AR1	ENST00000904894.1		c.*146A>G		3_prime_UTR	Exon 2 of 2	ENSP00000574953.1
	C3AR1	ENST00000904895.1		c.*146A>G		3_prime_UTR	Exon 2 of 2	ENSP00000574954.1

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

African (AFR) AF: 0.357 AC: 6262 AN: 17554

American (AMR) AF: 0.273 AC: 6874 AN: 25148

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 4051 AN: 15550

East Asian (EAS) AF: 0.188 AC: 6591 AN: 35134

South Asian (SAS) AF: 0.328 AC: 16760 AN: 51170

European-Finnish (FIN) AF: 0.293 AC: 11280 AN: 38494

Middle Eastern (MID) AF: 0.308 AC: 730 AN: 2368

European-Non Finnish (NFE) AF: 0.305 AC: 145345 AN: 477062

Other (OTH) AF: 0.299 AC: 10131 AN: 33874

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

African (AFR) AF: 0.354 AC: 14670 AN: 41436

American (AMR) AF: 0.319 AC: 4874 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.190 AC: 985 AN: 5174

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3072 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20642 AN: 67974

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.308 Hom.: 30747

Bravo AF: 0.318

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.36
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs7842; hg19: chr12-8211187;