rs1048118

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145252.3(CFP):c.1284C>T(p.Asn428Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,206,924 control chromosomes in the GnomAD database, including 23,912 homozygotes. There are 94,035 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 2214 hom., 6963 hem., cov: 21)

Exomes 𝑓: 0.24 ( 21698 hom. 87072 hem. )

Consequence

CFP
NM_001145252.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.15

Publications

10 publications found

Variant links:

Genes affected

CFP (HGNC:8864): (complement factor properdin) This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Feb 2009]

CFP Gene-Disease associations (from GenCC):

properdin deficiency, X-linked
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

CFP links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-47624401-G-A is Benign according to our data. Variant chrX-47624401-G-A is described in ClinVar as Benign. ClinVar VariationId is 402535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFP	NM_001145252.3 link	c.1284C>T	p.Asn428Asn	synonymous_variant	Exon 9 of 9	ENST00000396992.8	NP_001138724.1	P27918A0A0S2Z4I5
CFP	NM_002621.2 link	c.1284C>T	p.Asn428Asn	synonymous_variant	Exon 10 of 10		NP_002612.1	P27918A0A0S2Z4I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8 link	c.1284C>T	p.Asn428Asn	synonymous_variant	Exon 9 of 9	1	NM_001145252.3	ENSP00000380189.3		P27918

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

25063

AN:

109172

Hom.:

2211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.223

AC:

40806

AN:

182837

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.00808

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.239

AC:

262418

AN:

1097704

Hom.:

21698

Cov.:

AF XY:

0.240

AC XY:

87072

AN XY:

363124

show subpopulations

African (AFR)

AF:

0.231

AC:

6099

AN:

26394

American (AMR)

AF:

0.248

AC:

8736

AN:

35175

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

3061

AN:

19375

East Asian (EAS)

AF:

0.0155

AC:

467

AN:

30197

South Asian (SAS)

AF:

0.261

AC:

14124

AN:

54134

European-Finnish (FIN)

AF:

0.212

AC:

8598

AN:

40505

Middle Eastern (MID)

AF:

0.242

AC:

1002

AN:

4133

European-Non Finnish (NFE)

AF:

0.249

AC:

209782

AN:

841714

Other (OTH)

AF:

0.229

AC:

10549

AN:

46077

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7208

14416

21625

28833

36041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7460

14920

22380

29840

37300

<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:

0.230

AC:

25074

AN:

109220

Hom.:

2214

Cov.:

AF XY:

0.221

AC XY:

6963

AN XY:

31550

show subpopulations

African (AFR)

AF:

0.227

AC:

6796

AN:

29905

American (AMR)

AF:

0.249

AC:

2559

AN:

10262

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

451

AN:

2628

East Asian (EAS)

AF:

0.0106

AC:

AN:

3478

South Asian (SAS)

AF:

0.232

AC:

579

AN:

2493

European-Finnish (FIN)

AF:

0.198

AC:

1113

AN:

5633

Middle Eastern (MID)

AF:

0.199

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.249

AC:

13059

AN:

52442

Other (OTH)

AF:

0.219

AC:

327

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

679

1358

2038

2717

3396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.240

Hom.:

21864

Bravo

AF:

0.231

EpiCase

AF:

0.233

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.31

(source)

DANN

Benign

0.91

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over