6-31948623-A-G

Variant names:

• chr6-31948623-A-G
• rs537160
• NM_001710.6:c.1036+111A>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.1036+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,558,018 control chromosomes in the GnomAD database, including 370,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40872 hom., cov: 31)
  • Exomes 𝑓: 0.68 (330058 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600
• Publications: 72 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
• C3 glomerulonephritis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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 6-31948623-A-G is Benign according to our data. Variant chr6-31948623-A-G is described in ClinVar as Benign. ClinVar VariationId is 1285918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.84 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.1036+111A>G		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.1036+111A>G		intron	N/A	ENSP00000416561.2	P00751-1
	ENSG00000244255	ENST00000456570.5	TSL:2	c.2542+111A>G		intron	N/A	ENSP00000410815.1	B4E1Z4
	ENSG00000244255	ENST00000477310.1	TSL:5	c.2089+111A>G		intron	N/A	ENSP00000418996.1	E7ETN3

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110561 AN: 151928 Hom.: 40834 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.679 AC: 955050 AN: 1405972 Hom.: 330058 AF XY: 0.688 AC XY: 482739 AN XY: 701636

African (AFR) AF: 0.829 AC: 27010 AN: 32598

American (AMR) AF: 0.709 AC: 31010 AN: 43710

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 22868 AN: 25754

East Asian (EAS) AF: 0.645 AC: 25418 AN: 39388

South Asian (SAS) AF: 0.879 AC: 74377 AN: 84600

European-Finnish (FIN) AF: 0.685 AC: 31086 AN: 45412

Middle Eastern (MID) AF: 0.895 AC: 4821 AN: 5384

European-Non Finnish (NFE) AF: 0.652 AC: 697928 AN: 1070478

Other (OTH) AF: 0.691 AC: 40532 AN: 58648

GnomAD4 genome AF: 0.728 AC: 110653 AN: 152046 Hom.: 40872 Cov.: 31 AF XY: 0.731 AC XY: 54340 AN XY: 74302

African (AFR) AF: 0.816 AC: 33827 AN: 41476

American (AMR) AF: 0.715 AC: 10930 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3035 AN: 5156

South Asian (SAS) AF: 0.862 AC: 4152 AN: 4816

European-Finnish (FIN) AF: 0.702 AC: 7416 AN: 10564

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45619 AN: 67968

Other (OTH) AF: 0.777 AC: 1640 AN: 2112

Alfa AF: 0.693 Hom.: 152062

Bravo AF: 0.733

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.0060
PromoterAI		0.033	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs537160;

hg19: chr6-31916400;

COSMIC: COSV54961796;

COSMIC: COSV54961796;