NM_000064.4:c.2421G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000064.4(C3):c.2421G>C(p.Val807Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,595,750 control chromosomes in the GnomAD database, including 329,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33429 hom., cov: 32)

Exomes 𝑓: 0.64 ( 296284 hom. )

Consequence

C3
NM_000064.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.138

Publications

36 publications found

Variant links:

Genes affected

C3 (HGNC:1318): (complement C3) Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]

C3 Gene-Disease associations (from GenCC):

atypical hemolytic-uremic syndrome with C3 anomaly
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
complement component 3 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
C3 glomerulonephritis
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

C3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-6702146-C-G is Benign according to our data. Variant chr19-6702146-C-G is described in ClinVar as Benign. ClinVar VariationId is 330305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.138 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	NM_000064.4	MANE Select	c.2421G>C	p.Val807Val	synonymous	Exon 19 of 41	NP_000055.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
C3	ENST00000245907.11	TSL:1 MANE Select	c.2421G>C	p.Val807Val	synonymous	Exon 19 of 41	ENSP00000245907.4
C3	ENST00000695654.1		c.1545G>C	p.Val515Val	synonymous	Exon 11 of 32	ENSP00000512085.1
C3	ENST00000695652.1		c.2298G>C	p.Val766Val	synonymous	Exon 19 of 29	ENSP00000512083.1

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100195

AN:

151948

Hom.:

33391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.676

GnomAD2 exomes

AF:

0.674

AC:

168682

AN:

250406

AF XY:

0.666

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.811

Gnomad ASJ exome

AF:

0.597

Gnomad EAS exome

AF:

0.838

Gnomad FIN exome

AF:

0.563

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.664

GnomAD4 exome

AF:

0.636

AC:

918576

AN:

1443684

Hom.:

296284

Cov.:

AF XY:

0.637

AC XY:

458040

AN XY:

719452

show subpopulations

African (AFR)

AF:

0.711

AC:

23444

AN:

32960

American (AMR)

AF:

0.800

AC:

35769

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

15390

AN:

25998

East Asian (EAS)

AF:

0.865

AC:

34281

AN:

39612

South Asian (SAS)

AF:

0.706

AC:

60665

AN:

85896

European-Finnish (FIN)

AF:

0.565

AC:

29470

AN:

52146

Middle Eastern (MID)

AF:

0.673

AC:

3845

AN:

5712

European-Non Finnish (NFE)

AF:

0.617

AC:

676951

AN:

1096832

Other (OTH)

AF:

0.648

AC:

38761

AN:

59834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

16444

32888

49332

65776

82220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18172

36344

54516

72688

90860

<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:

0.660

AC:

100290

AN:

152066

Hom.:

33429

Cov.:

AF XY:

0.662

AC XY:

49190

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.705

AC:

29223

AN:

41452

American (AMR)

AF:

0.736

AC:

11245

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2126

AN:

3468

East Asian (EAS)

AF:

0.842

AC:

4354

AN:

5174

South Asian (SAS)

AF:

0.712

AC:

3437

AN:

4828

European-Finnish (FIN)

AF:

0.569

AC:

6013

AN:

10572

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41869

AN:

67982

Other (OTH)

AF:

0.672

AC:

1422

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1748

3496

5244

6992

8740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.635

Hom.:

20753

Bravo

AF:

0.675

Asia WGS

AF:

0.765

AC:

2659

AN:

3478

EpiCase

AF:

0.635

EpiControl

AF:

0.633

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 9 (2)

Complement component 3 deficiency (2)

not provided (2)

not specified (2)

Atypical hemolytic-uremic syndrome with C3 anomaly (1)

Atypical hemolytic-uremic syndrome;C3151071:Complement component 3 deficiency;C4055342:C3 glomerulonephritis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.2

(source)

DANN

Benign

0.69

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over