rs641153

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.95G>A(p.Arg32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 1,612,870 control chromosomes in the GnomAD database, including 8,814 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1207 hom., cov: 31)

Exomes 𝑓: 0.097 ( 7607 hom. )

Consequence

CFB
NM_001710.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.31

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:

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=0.001252532).

BP6

Variant 6-31946403-G-A is Benign according to our data. Variant chr6-31946403-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 16075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31946403-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6 link	c.95G>A	p.Arg32Gln	missense_variant	Exon 2 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.95G>A	p.Arg32Gln	missense_variant	Exon 2 of 18	1	NM_001710.6	ENSP00000416561.2		P00751-1
ENSG00000244255	ENST00000456570.5 link	c.1601G>A	p.Arg534Gln	missense_variant	Exon 14 of 30	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17666

AN:

152026

Hom.:

1209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0574

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0579

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.0960

AC:

23669

AN:

246556

AF XY:

0.0987

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0702

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.0619

Gnomad FIN exome

AF:

0.0635

Gnomad NFE exome

AF:

0.0902

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0971

AC:

141800

AN:

1460726

Hom.:

7607

Cov.:

AF XY:

0.0979

AC XY:

71130

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.188

AC:

6288

AN:

33480

Gnomad4 AMR exome

AF:

0.0734

AC:

3283

AN:

44720

Gnomad4 ASJ exome

AF:

0.0555

AC:

1451

AN:

26136

Gnomad4 EAS exome

AF:

0.0736

AC:

2923

AN:

39700

Gnomad4 SAS exome

AF:

0.149

AC:

12841

AN:

86258

Gnomad4 FIN exome

AF:

0.0650

AC:

3402

AN:

52310

Gnomad4 NFE exome

AF:

0.0942

AC:

104704

AN:

1111972

Gnomad4 Remaining exome

AF:

0.108

AC:

6511

AN:

60382

Heterozygous variant carriers

8281

16562

24844

33125

41406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

4022

8044

12066

16088

20110

<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:

0.116

AC:

17688

AN:

152144

Hom.:

1207

Cov.:

AF XY:

0.114

AC XY:

8486

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.191

AC:

0.190613

AN:

0.190613

Gnomad4 AMR

AF:

0.100

AC:

0.100118

AN:

0.100118

Gnomad4 ASJ

AF:

0.0574

AC:

0.0574149

AN:

0.0574149

Gnomad4 EAS

AF:

0.0624

AC:

0.0623789

AN:

0.0623789

Gnomad4 SAS

AF:

0.133

AC:

0.133085

AN:

0.133085

Gnomad4 FIN

AF:

0.0579

AC:

0.0579245

AN:

0.0579245

Gnomad4 NFE

AF:

0.0902

AC:

0.0901738

AN:

0.0901738

Gnomad4 OTH

AF:

0.128

AC:

0.128436

AN:

0.128436

Heterozygous variant carriers

805

1610

2414

3219

4024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0999

Hom.:

1336

Bravo

AF:

0.123

TwinsUK

AF:

0.0939

AC:

348

ALSPAC

AF:

0.102

AC:

394

ESP6500AA

AF:

0.177

AC:

535

ESP6500EA

AF:

0.0866

AC:

469

ExAC

AF:

0.0977

AC:

11498

Asia WGS

AF:

0.154

AC:

534

AN:

3478

EpiCase

AF:

0.0864

EpiControl

AF:

0.0878

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28173125, 16518403, 19255449, 21555552, 16936732, 23112567, 18806293) -

Macular degeneration

Benign:3

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:Likely 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

- -

Atypical hemolytic-uremic syndrome

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

- -

BF*FA/S

Benign:1

Oct 30, 2017

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Complement component 2 deficiency;C3809653:Age related macular degeneration 14

Benign:1

Apr 22, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Age related macular degeneration 14

Benign:1

Aug 12, 2016

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

- -

Focal segmental glomerulosclerosis

Benign:1

Sep 27, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atypical hemolytic-uremic syndrome with B factor anomaly

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Factor B fast/slow polymorphism

Benign:1

Jan 01, 1994

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.036

DANN

Benign

0.58

DEOGEN2

Benign

0.030

.;.;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.45

T;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.49

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0050

.;.;B

Vest4

0.033

MPC

0.54

ClinPred

0.0030

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.018

gMVP

0.45

Mutation Taster

=99/1

polymorphism (auto)

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

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