6-31951801-A-G

Variant names:

• chr6-31951801-A-G
• rs2072633
• NM_001710.6:c.2140-74A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001710.6(CFB):​c.2140-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,607,806 control chromosomes in the GnomAD database, including 263,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27070 hom., cov: 32)
  • Exomes 𝑓: 0.56 (236755 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0460
• Publications: 96 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: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• complement factor b deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000244255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-31951801-A-G is Benign according to our data. Variant chr6-31951801-A-G is described in ClinVar as Benign. ClinVar VariationId is 1209734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFB	NM_001710.6	MANE Select	c.2140-74A>G		intron	N/A	NP_001701.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFB	ENST00000425368.7	TSL:1 MANE Select	c.2140-74A>G		intron	N/A	ENSP00000416561.2
	ENSG00000244255	ENST00000456570.5	TSL:2	c.3646-74A>G		intron	N/A	ENSP00000410815.1
	CFB	ENST00000498317.1	TSL:2	n.306A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90128 AN: 151994 Hom.: 27056 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.564 AC: 821590 AN: 1455694 Hom.: 236755 Cov.: 32 AF XY: 0.573 AC XY: 414782 AN XY: 724444

African (AFR) AF: 0.630 AC: 21012 AN: 33340

American (AMR) AF: 0.598 AC: 26703 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 19182 AN: 26108

East Asian (EAS) AF: 0.506 AC: 20074 AN: 39686

South Asian (SAS) AF: 0.727 AC: 62629 AN: 86090

European-Finnish (FIN) AF: 0.619 AC: 32875 AN: 53114

Middle Eastern (MID) AF: 0.791 AC: 3862 AN: 4882

European-Non Finnish (NFE) AF: 0.543 AC: 601718 AN: 1107674

Other (OTH) AF: 0.558 AC: 33535 AN: 60110

GnomAD4 genome AF: 0.593 AC: 90193 AN: 152112 Hom.: 27070 Cov.: 32 AF XY: 0.600 AC XY: 44597 AN XY: 74368

African (AFR) AF: 0.615 AC: 25524 AN: 41502

American (AMR) AF: 0.577 AC: 8814 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2532 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2453 AN: 5166

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4824

European-Finnish (FIN) AF: 0.642 AC: 6793 AN: 10578

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38418 AN: 67978

Other (OTH) AF: 0.607 AC: 1280 AN: 2108

Alfa AF: 0.582 Hom.: 111630

Bravo AF: 0.588

Asia WGS AF: 0.528 AC: 1839 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Complement factor b deficiency Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Atypical hemolytic-uremic syndrome with B factor anomaly Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Atypical hemolytic-uremic syndrome Benign:1

Sep 26, 2025

Genomenon, Inc, Genomenon, Inc

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

CFB c.2140-74A>G is an intronic variant located in intron 17. This variant has been reported in the published literature (PMID:29682912). This variant is present at high allele frequency in population databases. In conclusion, we classify CFB c.2140-74A>G as a benign variant.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.53
PhyloP100		-0.046
PromoterAI		0.00080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2072633; hg19: chr6-31919578;