rs761962858

Positions:

chrX-47628269-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 235395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47628269-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111812

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

AN XY:

33974

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

GnomAD3 exomes

AF:

0.00114

AC:

195

AN:

170702

Hom.:

AF XY:

0.00161

AC XY:

AN XY:

57724

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 SAS exome

AF:

0.00990

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

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000998

Gnomad4 SAS exome

AF:

0.00983

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.000718

GnomAD4 genome

AF:

0.000206

AC:

AN:

111864

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

AN XY:

34036

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00782

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 30, 2015	- -

CFP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over