rs2230204

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1692G>A(p.Val564Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,612,958 control chromosomes in the GnomAD database, including 86,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11312 hom., cov: 29)

Exomes 𝑓: 0.31 ( 74758 hom. )

Consequence

C3
NM_000064.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.18

Publications

30 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
C3 glomerulonephritis
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

C3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000064.4, 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-6709837-C-T is Benign according to our data. Variant chr19-6709837-C-T is described in ClinVar as Benign. ClinVar VariationId is 330321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	NM_000064.4	MANE Select	c.1692G>A	p.Val564Val	synonymous	Exon 14 of 41	NP_000055.2	P01024

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C3	ENST00000245907.11	TSL:1 MANE Select	c.1692G>A	p.Val564Val	synonymous	Exon 14 of 41	ENSP00000245907.4	P01024
C3	ENST00000952696.1		c.1692G>A	p.Val564Val	synonymous	Exon 14 of 42	ENSP00000622755.1
C3	ENST00000879543.1		c.1692G>A	p.Val564Val	synonymous	Exon 14 of 41	ENSP00000549602.1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56132

AN:

151510

Hom.:

11309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.355

GnomAD2 exomes

AF:

0.353

AC:

88578

AN:

251044

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.313

AC:

457348

AN:

1461330

Hom.:

74758

Cov.:

AF XY:

0.315

AC XY:

228798

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.532

AC:

17814

AN:

33474

American (AMR)

AF:

0.397

AC:

17735

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7805

AN:

26134

East Asian (EAS)

AF:

0.478

AC:

18992

AN:

39692

South Asian (SAS)

AF:

0.441

AC:

38038

AN:

86256

European-Finnish (FIN)

AF:

0.306

AC:

16274

AN:

53134

Middle Eastern (MID)

AF:

0.252

AC:

1454

AN:

5760

European-Non Finnish (NFE)

AF:

0.288

AC:

319866

AN:

1111786

Other (OTH)

AF:

0.321

AC:

19370

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16428

32856

49284

65712

82140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11030

22060

33090

44120

55150

<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:

0.370

AC:

56177

AN:

151628

Hom.:

11312

Cov.:

AF XY:

0.373

AC XY:

27640

AN XY:

74082

show subpopulations

African (AFR)

AF:

0.523

AC:

21562

AN:

41262

American (AMR)

AF:

0.363

AC:

5522

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1051

AN:

3460

East Asian (EAS)

AF:

0.464

AC:

2388

AN:

5144

South Asian (SAS)

AF:

0.431

AC:

2068

AN:

4798

European-Finnish (FIN)

AF:

0.311

AC:

3274

AN:

10524

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19294

AN:

67918

Other (OTH)

AF:

0.356

AC:

750

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1642

3284

4926

6568

8210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.324

Hom.:

19698

Bravo

AF:

0.382

Asia WGS

AF:

0.440

AC:

1527

AN:

3478

EpiCase

AF:

0.278

EpiControl

AF:

0.287

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Age related macular degeneration 9 (2)

Complement component 3 deficiency (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

-0.60

CADD

Benign

8.0

(source)

DANN

Benign

0.67

PhyloP100

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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