rs7954916

Positions:

• chr12-8065796-C-A
• chr12-8065796-C-T

Variant summary

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

The NM_004054.4(C3AR1):​c.-11+482G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,576 control chromosomes in the GnomAD database, including 5,103 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 0.25 (5103 hom., cov: 31)
• Consequence: C3AR1 NM_004054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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 (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3AR1	NM_004054.4	c.-11+482G>T		intron_variant		ENST00000307637.5	NP_004045.1
C3AR1	NM_001326475.2	c.-8+482G>T		intron_variant			NP_001313404.1
C3AR1	NM_001326477.2	c.-11+425G>T		intron_variant			NP_001313406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5	c.-11+482G>T		intron_variant		1	NM_004054.4	ENSP00000302079.4
C3AR1	ENST00000546241.1	c.-11+425G>T		intron_variant		4		ENSP00000444500.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38248 AN: 151458 Hom.: 5102 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.252 AC: 38270 AN: 151576 Hom.: 5103 Cov.: 31 AF XY: 0.252 AC XY: 18649 AN XY: 74038

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.263

Alfa AF: 0.278 Hom.: 5345

Bravo AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.62

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: rs7954916; hg19: chr12-8218392;