6-31945661-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000063.6(C2):c.*304A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000873 in 538,416 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

C2
NM_000063.6 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -2.04

Publications

0 publications found

Variant links:

Genes affected

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 links:

ENSG00000244255 (HGNC:):

ENSG00000244255 links:

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), ClinGen, Ambry Genetics
complement factor b deficiency
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
C3 glomerulonephritis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CFB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 6-31945661-A-G is Benign according to our data. Variant chr6-31945661-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 356265.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000063.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2	NM_000063.6	MANE Select	c.*304A>G	3_prime_UTR	Exon 18 of 18	NP_000054.2
C2	NM_001282458.2		c.*304A>G	3_prime_UTR	Exon 18 of 18	NP_001269387.1	A0A0G2JL69
C2	NM_001145903.3		c.*304A>G	3_prime_UTR	Exon 16 of 16	NP_001139375.1	P06681-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2	ENST00000299367.10	TSL:1 MANE Select	c.*304A>G	3_prime_UTR	Exon 18 of 18	ENSP00000299367.5	P06681-1
ENSG00000244255	ENST00000456570.5	TSL:2	c.1571-712A>G	intron	N/A	ENSP00000410815.1	B4E1Z4
C2	ENST00000447952.7	TSL:3	c.*304A>G	3_prime_UTR	Exon 17 of 17	ENSP00000391354.3	F2Z3N2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000958

AC:

AN:

386174

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

202370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11386

American (AMR)

AF:

0.00

AC:

AN:

16610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12066

East Asian (EAS)

AF:

0.0000387

AC:

AN:

25808

South Asian (SAS)

AF:

0.00

AC:

AN:

41206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1710

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

231282

Other (OTH)

AF:

0.0000877

AC:

AN:

22812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68006

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000869

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 14 (1)

Atypical hemolytic-uremic syndrome (1)

Complement component 2 deficiency (1)

Macular degeneration (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.028

(source)

DANN

Benign

0.71

PhyloP100

-2.0

PromoterAI

0.23

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over