Genetic Variant C3AR1:c.*77G>A (chr12-8058660-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004054.4(C3AR1):c.*77G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,473,644 control chromosomes in the GnomAD database, including 868 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 0.035 ( 244 hom., cov: 32)

Exomes 𝑓: 0.010 ( 624 hom. )

Consequence

C3AR1
NM_004054.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.702

Publications

3 publications found

Variant links:

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]

C3AR1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004054.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C3AR1	NM_004054.4	MANE Select	c.*77G>A	3_prime_UTR	Exon 2 of 2	NP_004045.1	A8K2H7
C3AR1	NM_001326475.2		c.*77G>A	3_prime_UTR	Exon 2 of 2	NP_001313404.1	A8K2H7
C3AR1	NM_001326477.2		c.*77G>A	3_prime_UTR	Exon 2 of 2	NP_001313406.1	Q16581

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C3AR1	ENST00000307637.5	TSL:1 MANE Select	c.*77G>A	3_prime_UTR	Exon 2 of 2	ENSP00000302079.4	Q16581
C3AR1	ENST00000904894.1		c.*77G>A	3_prime_UTR	Exon 2 of 2	ENSP00000574953.1
C3AR1	ENST00000904895.1		c.*77G>A	3_prime_UTR	Exon 2 of 2	ENSP00000574954.1

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5352

AN:

152190

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0608

Gnomad SAS

AF:

0.0991

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0102

AC:

13417

AN:

1321336

Hom.:

624

Cov.:

AF XY:

0.0118

AC XY:

7668

AN XY:

652024

show subpopulations

African (AFR)

AF:

0.100

AC:

2948

AN:

29460

American (AMR)

AF:

0.0220

AC:

705

AN:

32032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20292

East Asian (EAS)

AF:

0.0538

AC:

2086

AN:

38758

South Asian (SAS)

AF:

0.0899

AC:

6307

AN:

70132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49824

Middle Eastern (MID)

AF:

0.00718

AC:

AN:

3622

European-Non Finnish (NFE)

AF:

0.000406

AC:

415

AN:

1022386

Other (OTH)

AF:

0.0170

AC:

930

AN:

54830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

631

1261

1892

2522

3153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0352

AC:

5356

AN:

152308

Hom.:

244

Cov.:

AF XY:

0.0360

AC XY:

2678

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.100

AC:

4159

AN:

41544

American (AMR)

AF:

0.0199

AC:

304

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0609

AC:

316

AN:

5188

South Asian (SAS)

AF:

0.0983

AC:

474

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68044

Other (OTH)

AF:

0.0246

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

237

475

712

950

1187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.0700

AC:

246

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.40

(source)

DANN

Benign

0.81

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over