dbSNP rs11567805: C3AR1:p.Leu70Leu (chr12-8059976-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004054.4(C3AR1):c.210C>T(p.Leu70Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,614,098 control chromosomes in the GnomAD database, including 855 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 0.029 ( 175 hom., cov: 32)

Exomes 𝑓: 0.010 ( 680 hom. )

Consequence

C3AR1
NM_004054.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3AR1	NM_004054.4 link	c.210C>T	p.Leu70Leu	synonymous_variant	Exon 2 of 2	ENST00000307637.5	NP_004045.1	Q16581A8K2H7
C3AR1	NM_001326475.2 link	c.210C>T	p.Leu70Leu	synonymous_variant	Exon 2 of 2		NP_001313404.1	Q16581A8K2H7
C3AR1	NM_001326477.2 link	c.210C>T	p.Leu70Leu	synonymous_variant	Exon 2 of 2		NP_001313406.1	Q16581A8K2H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5 link	c.210C>T	p.Leu70Leu	synonymous_variant	Exon 2 of 2	1	NM_004054.4	ENSP00000302079.4		Q16581
C3AR1	ENST00000546241.1 link	c.210C>T	p.Leu70Leu	synonymous_variant	Exon 2 of 2	4		ENSP00000444500.1		F5GZE6

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4379

AN:

152114

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0603

Gnomad SAS

AF:

0.0971

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.0251

AC:

6316

AN:

251332

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0635

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000739

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0102

AC:

14957

AN:

1461866

Hom.:

680

Cov.:

AF XY:

0.0121

AC XY:

8781

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0797

AC:

2668

AN:

33478

American (AMR)

AF:

0.0213

AC:

951

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0539

AC:

2139

AN:

39700

South Asian (SAS)

AF:

0.0897

AC:

7736

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000390

AC:

434

AN:

1112004

Other (OTH)

AF:

0.0164

AC:

990

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

889

1779

2668

3558

4447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0288

AC:

4381

AN:

152232

Hom.:

175

Cov.:

AF XY:

0.0296

AC XY:

2206

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0782

AC:

3246

AN:

41506

American (AMR)

AF:

0.0175

AC:

268

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0605

AC:

313

AN:

5176

South Asian (SAS)

AF:

0.0963

AC:

464

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68018

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

199

397

596

794

993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.00971

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.4

(source)

DANN

Benign

0.78

PhyloP100

1.7

Mutation Taster

=83/17

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over