rs1048709

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001710.6(CFB):c.450A>G(p.Arg150=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 356272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31947158-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CFB	NM_001710.6 linkuse as main transcript	c.450A>G	p.Arg150=	synonymous_variant	3/18	ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7 linkuse as main transcript	c.450A>G	p.Arg150=	synonymous_variant	3/18	1	NM_001710.6	ENSP00000416561	P1	P00751-1

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

GnomAD3 exomes

AF:

0.824

AC:

203076

AN:

246520

Hom.:

84415

AF XY:

0.832

AC XY:

111769

AN XY:

134392

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 SAS exome

AF:

0.906

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

Gnomad4 AFR exome

AF:

0.967

Gnomad4 AMR exome

AF:

0.765

Gnomad4 ASJ exome

AF:

0.946

Gnomad4 EAS exome

AF:

0.718

Gnomad4 SAS exome

AF:

0.904

Gnomad4 FIN exome

AF:

0.798

Gnomad4 NFE exome

AF:

0.807

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.852

AC:

129579

AN:

152074

Hom.:

55633

Cov.:

AF XY:

0.850

AC XY:

63147

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.957

Gnomad4 AMR

AF:

0.782

Gnomad4 ASJ

AF:

0.947

Gnomad4 EAS

AF:

0.696

Gnomad4 SAS

AF:

0.906

Gnomad4 FIN

AF:

0.812

Gnomad4 NFE

AF:

0.811

Gnomad4 OTH

AF:

0.877

Alfa

AF:

0.835

Hom.:

92866

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Atypical hemolytic-uremic syndrome with B factor anomaly

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

Macular degeneration

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Complement factor b deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Complement component 2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over