6-31951083-A-G

Variant names:

• chr6-31951083-A-G
• rs1270942
• NM_001710.6:c.1856-61A>G

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.1856-61A>G 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 1,591,678 control chromosomes in the GnomAD database, including 9,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (521 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9450 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.554
• Publications: 115 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-31951083-A-G is Benign according to our data. Variant chr6-31951083-A-G is described in ClinVar as Benign. ClinVar VariationId is 1246301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.1856-61A>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.1856-61A>G		intron	N/A	ENSP00000416561.2
	ENSG00000244255	ENST00000456570.5	TSL:2	c.3362-61A>G		intron	N/A	ENSP00000410815.1
	CFB	ENST00000482312.1	TSL:2	n.210A>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11077 AN: 152134 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.102 AC: 147118 AN: 1439424 Hom.: 9450 Cov.: 27 AF XY: 0.0987 AC XY: 70793 AN XY: 717458

African (AFR) AF: 0.0556 AC: 1837 AN: 33018

American (AMR) AF: 0.0238 AC: 1066 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0399 AC: 1037 AN: 25988

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39560

South Asian (SAS) AF: 0.000338 AC: 29 AN: 85686

European-Finnish (FIN) AF: 0.0808 AC: 4222 AN: 52232

Middle Eastern (MID) AF: 0.00798 AC: 41 AN: 5138

European-Non Finnish (NFE) AF: 0.122 AC: 133592 AN: 1093468

Other (OTH) AF: 0.0887 AC: 5290 AN: 59618

GnomAD4 genome AF: 0.0727 AC: 11075 AN: 152254 Hom.: 521 Cov.: 32 AF XY: 0.0676 AC XY: 5034 AN XY: 74448

African (AFR) AF: 0.0512 AC: 2127 AN: 41540

American (AMR) AF: 0.0338 AC: 517 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0788 AC: 836 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7274 AN: 67988

Other (OTH) AF: 0.0548 AC: 116 AN: 2116

Alfa AF: 0.0974 Hom.: 4020

Bravo AF: 0.0689

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.55
PromoterAI		0.064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1270942; hg19: chr6-31918860;