rs4151650

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001710.6(CFB):c.405C>T(p.Tyr135Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,613,052 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 17 hom. )

Consequence

CFB
NM_001710.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.260

Publications

3 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=-0.61).

BP6

Variant 6-31947113-C-T is Benign according to our data. Variant chr6-31947113-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1677/152284) while in subpopulation AFR AF = 0.0349 (1448/41546). AF 95% confidence interval is 0.0334. There are 30 homozygotes in GnomAd4. There are 814 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6 link	c.405C>T	p.Tyr135Tyr	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.405C>T	p.Tyr135Tyr	synonymous_variant	Exon 3 of 18	1	NM_001710.6	ENSP00000416561.2		P00751-1
ENSG00000244255	ENST00000456570.5 link	c.1911C>T	p.Tyr637Tyr	synonymous_variant	Exon 15 of 30	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1673

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00360

AC:

887

AN:

246608

AF XY:

0.00264

show subpopulations

Gnomad AFR exome

AF:

0.0342

Gnomad AMR exome

AF:

0.00638

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00157

AC:

2292

AN:

1460768

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1043

AN XY:

726700

show subpopulations

African (AFR)

AF:

0.0288

AC:

963

AN:

33480

American (AMR)

AF:

0.00644

AC:

288

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.000301

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000268

AC:

AN:

52310

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000692

AC:

770

AN:

1112006

Other (OTH)

AF:

0.00333

AC:

201

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0110

AC:

1677

AN:

152284

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

814

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0349

AC:

1448

AN:

41546

American (AMR)

AF:

0.00810

AC:

124

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68028

Other (OTH)

AF:

0.0114

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00729

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.00160

ClinVar

Significance: Benign/Likely 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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Macular degeneration

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CFB-related disorder

Benign:1

Jul 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Atypical hemolytic-uremic syndrome with B factor anomaly

Benign:1

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. -

Atypical hemolytic-uremic syndrome

Benign:1

Aug 10, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.61

CADD

Benign

7.3

(source)

DANN

Benign

0.87

PhyloP100

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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