6-31948623-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.1036+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,558,018 control chromosomes in the GnomAD database, including 370,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40872 hom., cov: 31)
  • Exomes 𝑓: 0.68 (330058 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

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=-0.87).
• BP6: Variant 6-31948623-A-G is Benign according to our data. Variant chr6-31948623-A-G is described in ClinVar as [Benign]. Clinvar id is 1285918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFB	NM_001710.6	c.1036+111A>G		intron_variant		ENST00000425368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFB	ENST00000425368.7	c.1036+111A>G		intron_variant		1	NM_001710.6	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110561 AN: 151928 Hom.: 40834 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.679 AC: 955050 AN: 1405972 Hom.: 330058 AF XY: 0.688 AC XY: 482739 AN XY: 701636

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.888

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.879

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.691

GnomAD4 genome AF: 0.728 AC: 110653 AN: 152046 Hom.: 40872 Cov.: 31 AF XY: 0.731 AC XY: 54340 AN XY: 74302

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.777

Alfa AF: 0.698 Hom.: 61463

Bravo AF: 0.733

Asia WGS AF: 0.702 AC: 2441 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.3
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs537160; hg19: chr6-31916400; COSMIC: COSV54961796; COSMIC: COSV54961796;