Variant chr6-31946403-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001710.6(CFB):c.95G>T(p.Arg32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CFB
NM_001710.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088350505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6 linkuse as main transcript	c.95G>T	p.Arg32Leu	missense_variant	2/18	ENST00000425368.7	NP_001701.2	P00751-1A0A1U9X7H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7 linkuse as main transcript	c.95G>T	p.Arg32Leu	missense_variant	2/18	1	NM_001710.6	ENSP00000416561.2		P00751-1
ENSG00000244255	ENST00000456570.5 linkuse as main transcript	c.1601G>T	p.Arg534Leu	missense_variant	14/30	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246556

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460764

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.029

DANN

Benign

0.60

DEOGEN2

Benign

0.036

.;.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.44

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.27

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.089

MutPred

0.56

Loss of sheet (P = 0.0228);.;.;

MVP

0.32

MPC

0.58

ClinPred

0.12

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.043

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over