rs1270942

Positions:

• chr6-31951083-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001710.6(CFB):​c.1856-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,591,678 control chromosomes in the GnomAD database, including 9,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (521 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9450 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.554

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-31951083-A-G is Benign according to our data. Variant chr6-31951083-A-G is described in ClinVar as [Benign]. Clinvar id is 1246301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6	c.1856-61A>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.1856-61A>G		intron_variant		1	NM_001710.6	ENSP00000416561	P1

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11077 AN: 152134 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.102 AC: 147118 AN: 1439424 Hom.: 9450 Cov.: 27 AF XY: 0.0987 AC XY: 70793 AN XY: 717458

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000338

Gnomad4 FIN exome AF: 0.0808

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.0887

GnomAD4 genome AF: 0.0727 AC: 11075 AN: 152254 Hom.: 521 Cov.: 32 AF XY: 0.0676 AC XY: 5034 AN XY: 74448

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0925 Hom.: 1539

Bravo AF: 0.0689

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1270942; hg19: chr6-31918860;