rs4151667

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001710.6(CFB):c.26T>A(p.Leu9His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,613,062 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 108 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1430 hom. )

Consequence

CFB
NM_001710.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:18

Conservation

PhyloP100: 0.872

Publications

142 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: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
complement factor b deficiency
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
C3 glomerulonephritis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004921347).

BP6

Variant 6-31946247-T-A is Benign according to our data. Variant chr6-31946247-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 16077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001710.6. 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
	CFB	NM_001710.6	MANE Select	c.26T>A	p.Leu9His	missense	Exon 1 of 18	NP_001701.2	P00751-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFB	ENST00000425368.7	TSL:1 MANE Select	c.26T>A	p.Leu9His	missense	Exon 1 of 18	ENSP00000416561.2	P00751-1
ENSG00000244255	ENST00000456570.5	TSL:2	c.1571-126T>A		intron	N/A	ENSP00000410815.1	B4E1Z4
CFB	ENST00000885733.1		c.26T>A	p.Leu9His	missense	Exon 1 of 18	ENSP00000555792.1

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5164

AN:

152182

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0249

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.0220

Gnomad SAS

AF:

0.0559

Gnomad FIN

AF:

0.0553

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0387

AC:

9547

AN:

246528

AF XY:

0.0405

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0248

Gnomad EAS exome

AF:

0.0181

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0454

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0429

AC:

62642

AN:

1460762

Hom.:

1430

Cov.:

AF XY:

0.0435

AC XY:

31579

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.0124

AC:

414

AN:

33480

American (AMR)

AF:

0.0227

AC:

1016

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

671

AN:

26136

East Asian (EAS)

AF:

0.0221

AC:

877

AN:

39700

South Asian (SAS)

AF:

0.0517

AC:

4462

AN:

86258

European-Finnish (FIN)

AF:

0.0550

AC:

2879

AN:

52324

Middle Eastern (MID)

AF:

0.0270

AC:

156

AN:

5768

European-Non Finnish (NFE)

AF:

0.0448

AC:

49856

AN:

1111986

Other (OTH)

AF:

0.0383

AC:

2311

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4035

8070

12104

16139

20174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1848

3696

5544

7392

9240

<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:

0.0339

AC:

5169

AN:

152300

Hom.:

108

Cov.:

AF XY:

0.0348

AC XY:

2591

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0123

AC:

512

AN:

41578

American (AMR)

AF:

0.0253

AC:

387

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3470

East Asian (EAS)

AF:

0.0222

AC:

115

AN:

5174

South Asian (SAS)

AF:

0.0553

AC:

267

AN:

4828

European-Finnish (FIN)

AF:

0.0553

AC:

587

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0460

AC:

3130

AN:

68012

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

259

517

776

1034

1293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0362

Hom.:

Bravo

AF:

0.0292

TwinsUK

AF:

0.0440

AC:

163

ALSPAC

AF:

0.0368

AC:

142

ESP6500AA

AF:

0.00993

AC:

ESP6500EA

AF:

0.0423

AC:

229

ExAC

AF:

0.0386

AC:

4575

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Atypical hemolytic-uremic syndrome (3)

not specified (3)

Complement component 2 deficiency (2)

Macular degeneration (2)

Age related macular degeneration 14 (1)

Atypical hemolytic-uremic syndrome with B factor anomaly (1)

Atypical hemolytic-uremic syndrome with B factor anomaly;C3809653:Age related macular degeneration 14;C3809950:Complement factor b deficiency (1)

CFB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.075

Eigen

Benign

0.13

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0049

MetaSVM

Uncertain

-0.0028

MutationAssessor

Benign

0.69

PhyloP100

0.87

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.16

MPC

1.1

ClinPred

0.026

GERP RS

5.3

PromoterAI

0.013

Neutral

(source)

Varity_R

0.24

gMVP

0.66

Mutation Taster

=93/7

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

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

Computational scores

Splicing

Publications

Other links and lift over