rs4151650

Positions:

chr6-31947113-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001710.6(CFB):c.405C>T(p.Tyr135=) 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

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=-0.61).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6 linkuse as main transcript	c.405C>T	p.Tyr135=	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.405C>T	p.Tyr135=	synonymous_variant	3/18	1	NM_001710.6	ENSP00000416561	P1	P00751-1

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

GnomAD3 exomes

AF:

0.00360

AC:

887

AN:

246608

Hom.:

AF XY:

0.00264

AC XY:

355

AN XY:

134428

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 SAS exome

AF:

0.0000988

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

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.00644

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.000268

Gnomad4 NFE exome

AF:

0.000692

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.0110

AC:

1677

AN:

152284

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

814

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0349

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00445

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Macular degeneration

Benign:2

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

Complement component 2 deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

CFB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

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

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. -

Atypical hemolytic-uremic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.3

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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