rs774923308

Variant names:

• chr6-31946488-C-T
• rs774923308
• NM_001710.6:c.180C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31946488-C-T
• chr6-31946488-C-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001710.6(CFB):​c.180C>T​(p.Tyr60Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CFB NM_001710.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.121
• Publications: 2 publications found

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]

CFB Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with B factor anomaly

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• complement factor b deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• C3 glomerulonephritis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000244255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-31946488-C-T is Benign according to our data. Variant chr6-31946488-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1992553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.121 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001710.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFB	NM_001710.6	MANE Select	c.180C>T	p.Tyr60Tyr	synonymous	Exon 2 of 18	NP_001701.2	P00751-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFB	ENST00000425368.7	TSL:1 MANE Select	c.180C>T	p.Tyr60Tyr	synonymous	Exon 2 of 18	ENSP00000416561.2	P00751-1
	ENSG00000244255	ENST00000456570.5	TSL:2	c.1686C>T	p.Tyr562Tyr	synonymous	Exon 14 of 30	ENSP00000410815.1	B4E1Z4
	CFB	ENST00000885733.1		c.180C>T	p.Tyr60Tyr	synonymous	Exon 2 of 18	ENSP00000555792.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246648 AF XY: 0.00

Gnomad AFR exome AF: 0.0000661

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460766 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726702

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74294

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.9
DANN	Benign	0.90
PhyloP100		0.12
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs774923308; hg19: chr6-31914265;