rs541862

Variant names:

• chr6-31949174-T-C
• rs541862
• NM_001710.6:c.1169-69T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31949174-T-C
• chr6-31949174-T-G
• chr6-31949174-T-A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 74 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 -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 VariationId 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.

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.1169-69T>C		intron	N/A	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.1169-69T>C		intron	N/A	ENSP00000416561.2	P00751-1
	ENSG00000244255	ENST00000456570.5	TSL:2	c.2675-69T>C		intron	N/A	ENSP00000410815.1	B4E1Z4
	ENSG00000244255	ENST00000477310.1	TSL:5	c.2222-69T>C		intron	N/A	ENSP00000418996.1	E7ETN3

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

African (AFR) AF: 0.189 AC: 6034 AN: 31856

American (AMR) AF: 0.0743 AC: 3152 AN: 42416

Ashkenazi Jewish (ASJ) AF: 0.0555 AC: 1412 AN: 25424

East Asian (EAS) AF: 0.0738 AC: 2890 AN: 39174

South Asian (SAS) AF: 0.149 AC: 12412 AN: 83284

European-Finnish (FIN) AF: 0.0650 AC: 3399 AN: 52260

Middle Eastern (MID) AF: 0.0724 AC: 336 AN: 4642

European-Non Finnish (NFE) AF: 0.0944 AC: 98318 AN: 1041162

Other (OTH) AF: 0.109 AC: 6281 AN: 57562

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

African (AFR) AF: 0.193 AC: 8020 AN: 41522

American (AMR) AF: 0.102 AC: 1557 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.0625 AC: 324 AN: 5186

South Asian (SAS) AF: 0.134 AC: 647 AN: 4824

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10612

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6185 AN: 68014

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.0922 Hom.: 3021

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.72
PhyloP100		-2.5
PromoterAI		0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs541862; hg19: chr6-31916951;