rs541862

Positions:

• chr6-31949174-T-C

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.1169-69T>C 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 1,530,028 control chromosomes in the GnomAD database, including 8,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1235 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7258 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.47

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-31949174-T-C is Benign according to our data. Variant chr6-31949174-T-C is described in ClinVar as [Benign]. Clinvar id is 1283922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6	c.1169-69T>C		intron_variant		ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.1169-69T>C		intron_variant		1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.2675-69T>C		intron_variant		2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17868 AN: 152130 Hom.: 1237 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0974 AC: 134234 AN: 1377780 Hom.: 7258 Cov.: 22 AF XY: 0.0983 AC XY: 67629 AN XY: 688142

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.0555

Gnomad4 EAS exome AF: 0.0738

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0944

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.117 AC: 17889 AN: 152248 Hom.: 1235 Cov.: 32 AF XY: 0.115 AC XY: 8576 AN XY: 74444

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0884 Hom.: 1295

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 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	-0.87
CADD	Benign	0.037
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs541862; hg19: chr6-31916951;