rs761962858

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145252.3(CFP):c.236G>A(p.Arg79Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,206,119 control chromosomes in the GnomAD database, including 4 homozygotes. There are 354 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00059 ( 4 hom. 344 hem. )

Consequence

CFP
NM_001145252.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.25

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075173676).

BP6

Variant X-47628269-C-T is Benign according to our data. Variant chrX-47628269-C-T is described in ClinVar as Benign. ClinVar VariationId is 235395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000206 (23/111864) while in subpopulation SAS AF = 0.00782 (21/2687). AF 95% confidence interval is 0.00524. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFP	NM_001145252.3 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 3 of 9	ENST00000396992.8	NP_001138724.1	P27918A0A0S2Z4I5
CFP	NM_002621.2 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 4 of 10		NP_002612.1	P27918A0A0S2Z4I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 3 of 9	1	NM_001145252.3	ENSP00000380189.3		P27918

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111812

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:

0.000281

Gnomad SAS

AF:

0.00779

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00114

AC:

195

AN:

170702

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000148

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000589

AC:

644

AN:

1094255

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

344

AN XY:

360023

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26329

American (AMR)

AF:

0.00

AC:

AN:

34751

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19300

East Asian (EAS)

AF:

0.0000998

AC:

AN:

30050

South Asian (SAS)

AF:

0.00983

AC:

526

AN:

53506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40261

Middle Eastern (MID)

AF:

0.000726

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.0000929

AC:

AN:

839989

Other (OTH)

AF:

0.000718

AC:

AN:

45937

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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

100

<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:

0.000206

AC:

AN:

111864

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

AN XY:

34036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30752

American (AMR)

AF:

0.00

AC:

AN:

10619

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.000282

AC:

AN:

3551

South Asian (SAS)

AF:

0.00782

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53117

Other (OTH)

AF:

0.00

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0000811

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.00145

AC:

176

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 30, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CFP-related disorder

Benign:1

Jun 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0080

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.13

T;T;T

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.57

.;T;T

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.42

N;N;.

PhyloP100

-2.2

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.38

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.062

MutPred

0.50

Loss of MoRF binding (P = 0.0454);Loss of MoRF binding (P = 0.0454);Loss of MoRF binding (P = 0.0454);

MVP

0.10

MPC

0.74

ClinPred

0.0043

GERP RS

-5.6

Varity_R

0.091

gMVP

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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