rs2072633

Positions:

• chr6-31951801-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001710.6(CFB):​c.2140-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,607,806 control chromosomes in the GnomAD database, including 263,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27070 hom., cov: 32)
  • Exomes 𝑓: 0.56 (236755 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0460

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]

ENSG00000244255 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-31951801-A-G is Benign according to our data. Variant chr6-31951801-A-G is described in ClinVar as [Benign]. Clinvar id is 1209734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6	c.2140-74A>G		intron_variant		ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.2140-74A>G		intron_variant		1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.3646-74A>G		intron_variant		2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90128 AN: 151994 Hom.: 27056 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.564 AC: 821590 AN: 1455694 Hom.: 236755 Cov.: 32 AF XY: 0.573 AC XY: 414782 AN XY: 724444

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.593 AC: 90193 AN: 152112 Hom.: 27070 Cov.: 32 AF XY: 0.600 AC XY: 44597 AN XY: 74368

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.607

Alfa AF: 0.594 Hom.: 52903

Bravo AF: 0.588

Asia WGS AF: 0.528 AC: 1839 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Complement factor b deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Atypical hemolytic-uremic syndrome with B factor anomaly Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs2072633; hg19: chr6-31919578;