4-109762298-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000204.5(CFI):c.483-606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,238 control chromosomes in the GnomAD database, including 32,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 32296 hom., cov: 31)

Exomes 𝑓: 0.64 ( 72 hom. )

Consequence

CFI
NM_000204.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.789

Publications

6 publications found

Variant links:

Genes affected

CFI (HGNC:5394): (complement factor I) This gene encodes a serine proteinase that is essential for regulating the complement cascade. The encoded preproprotein is cleaved to produce both heavy and light chains, which are linked by disulfide bonds to form a heterodimeric glycoprotein. This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. Mutations in this gene have been associated with a predisposition to atypical hemolytic uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immune deposits and age-related macular degeneration are other conditions associated with mutations of this gene. [provided by RefSeq, Dec 2015]

CFI Gene-Disease associations (from GenCC):

atypical hemolytic-uremic syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
atypical hemolytic-uremic syndrome with I factor anomaly
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
complement factor I deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Doyne honeycomb retinal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
age related macular degeneration 13
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CFI links:

ENSG00000285330 (HGNC:):

ENSG00000285330 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-109762298-G-A is Benign according to our data. Variant chr4-109762298-G-A is described in ClinVar as Benign. ClinVar VariationId is 4280423.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFI	NM_000204.5	MANE Select	c.483-606C>T	intron	N/A	NP_000195.3
CFI	NM_001375278.1		c.483-606C>T	intron	N/A	NP_001362207.1
CFI	NM_001440985.1		c.483-606C>T	intron	N/A	NP_001427914.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFI	ENST00000394634.7	TSL:1 MANE Select	c.483-606C>T	intron	N/A	ENSP00000378130.2
ENSG00000285330	ENST00000645635.1		c.483-606C>T	intron	N/A	ENSP00000493607.1
CFI	ENST00000504853.3	TSL:2	n.294C>T	non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

96984

AN:

151806

Hom.:

32281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.758

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.645

GnomAD4 exome

AF:

0.636

AC:

201

AN:

316

Hom.:

Cov.:

AF XY:

0.603

AC XY:

111

AN XY:

184

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.571

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.635

AC:

179

AN:

282

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.639

AC:

97037

AN:

151922

Hom.:

32296

Cov.:

AF XY:

0.639

AC XY:

47451

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.441

AC:

18262

AN:

41396

American (AMR)

AF:

0.591

AC:

9019

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2405

AN:

3468

East Asian (EAS)

AF:

0.691

AC:

3571

AN:

5168

South Asian (SAS)

AF:

0.758

AC:

3648

AN:

4812

European-Finnish (FIN)

AF:

0.694

AC:

7321

AN:

10546

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.747

AC:

50764

AN:

67980

Other (OTH)

AF:

0.650

AC:

1364

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1677

3354

5030

6707

8384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.724

Hom.:

25633

Bravo

AF:

0.620

Asia WGS

AF:

0.692

AC:

2409

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CFI-related disorder

Benign:1

Sep 26, 2025

Genomenon, Inc, Genomenon, Inc

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

CFI c.483-606C>T is a deeply intronic variant located in intron 3. This variant is present at high allele frequency in population databases. In conclusion, we classify CFI c.483-606C>T as a benign variant.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.2

(source)

DANN

Benign

0.34

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over