rs1048709

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_001710.6(CFB):c.450A>G(p.Arg150Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,612,792 control chromosomes in the GnomAD database, including 543,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55633 hom., cov: 31)

Exomes 𝑓: 0.82 ( 488113 hom. )

Consequence

CFB
NM_001710.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.295

Publications

85 publications found

Variant links:

Genes affected

CFB (HGNC:1037): (complement factor B) This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

CFB Gene-Disease associations (from GenCC):

atypical hemolytic-uremic syndrome with B factor anomaly
Inheritance: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
complement factor b deficiency
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

CFB links:

ENSG00000244255 (HGNC:):

ENSG00000244255 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=-0.66).

BP6

Variant 6-31947158-A-G is Benign according to our data. Variant chr6-31947158-A-G is described in ClinVar as Benign. ClinVar VariationId is 356272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.295 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6 link	c.450A>G	p.Arg150Arg	synonymous_variant	Exon 3 of 18	ENST00000425368.7	NP_001701.2	P00751-1A0A1U9X7H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7 link	c.450A>G	p.Arg150Arg	synonymous_variant	Exon 3 of 18	1	NM_001710.6	ENSP00000416561.2		P00751-1
ENSG00000244255	ENST00000456570.5 link	c.1956A>G	p.Arg652Arg	synonymous_variant	Exon 15 of 30	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129465

AN:

151956

Hom.:

55578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.947

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.907

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.811

Gnomad OTH

AF:

0.876

GnomAD2 exomes

AF:

0.824

AC:

203076

AN:

246520

AF XY:

0.832

show subpopulations

Gnomad AFR exome

AF:

0.963

Gnomad AMR exome

AF:

0.756

Gnomad ASJ exome

AF:

0.947

Gnomad EAS exome

AF:

0.700

Gnomad FIN exome

AF:

0.804

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.835

GnomAD4 exome

AF:

0.816

AC:

1191706

AN:

1460718

Hom.:

488113

Cov.:

AF XY:

0.820

AC XY:

595898

AN XY:

726674

show subpopulations

African (AFR)

AF:

0.967

AC:

32367

AN:

33480

American (AMR)

AF:

0.765

AC:

34229

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.946

AC:

24735

AN:

26136

East Asian (EAS)

AF:

0.718

AC:

28510

AN:

39700

South Asian (SAS)

AF:

0.904

AC:

78002

AN:

86258

European-Finnish (FIN)

AF:

0.798

AC:

41713

AN:

52280

Middle Eastern (MID)

AF:

0.924

AC:

5332

AN:

5768

European-Non Finnish (NFE)

AF:

0.807

AC:

896938

AN:

1111992

Other (OTH)

AF:

0.826

AC:

49880

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14903

29807

44710

59614

74517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20826

41652

62478

83304

104130

<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:

0.852

AC:

129579

AN:

152074

Hom.:

55633

Cov.:

AF XY:

0.850

AC XY:

63147

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.957

AC:

39697

AN:

41500

American (AMR)

AF:

0.782

AC:

11944

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

3286

AN:

3470

East Asian (EAS)

AF:

0.696

AC:

3581

AN:

5142

South Asian (SAS)

AF:

0.906

AC:

4371

AN:

4824

European-Finnish (FIN)

AF:

0.812

AC:

8594

AN:

10580

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55151

AN:

67970

Other (OTH)

AF:

0.877

AC:

1845

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

954

1907

2861

3814

4768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.833

Hom.:

204282

Bravo

AF:

0.855

Asia WGS

AF:

0.839

AC:

2915

AN:

3478

EpiCase

AF:

0.835

EpiControl

AF:

0.844

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atypical hemolytic-uremic syndrome with B factor anomaly

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Macular degeneration

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Complement factor b deficiency

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Complement component 2 deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.29

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over