6-31946283-G-C

Variant names:

• chr6-31946283-G-C
• rs1291066881
• NM_001710.6:c.62G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001710.6(CFB):​c.62G>C​(p.Gly21Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFB NM_001710.6 missense, splice_region
• Scores: Splicing: ADA: 0.00002399
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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 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=0.14335904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6	c.62G>C	p.Gly21Ala	missense_variant, splice_region_variant	Exon 1 of 18	ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.62G>C	p.Gly21Ala	missense_variant, splice_region_variant	Exon 1 of 18	1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.1571-90G>C		intron_variant	Intron 13 of 29	2		ENSP00000410815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.80
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;N
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.028
Sift	Benign	0.50	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.010	.;B
Vest4		0.085
MutPred		0.51		Loss of glycosylation at S20 (P = 0.0436);Loss of glycosylation at S20 (P = 0.0436);
MVP		0.70
MPC		0.51
ClinPred		0.16	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1291066881; hg19: chr6-31914060;