rs1048118

Variant names:

• chrX-47624401-G-A
• rs1048118
• NM_001145252.3:c.1284C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.15

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]

ENSG00000283743 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 402535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47624401-G-A is described in Lovd as [Benign]. Variant chrX-47624401-G-A is described in Lovd as [Likely_benign].
• 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	c.1284C>T	p.Asn428Asn	synonymous_variant	Exon 9 of 9	ENST00000396992.8	NP_001138724.1
CFP	NM_002621.2	c.1284C>T	p.Asn428Asn	synonymous_variant	Exon 10 of 10		NP_002612.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.230 AC: 25063 AN: 109172 Hom.: 2211 Cov.: 21 AF XY: 0.221 AC XY: 6954 AN XY: 31492

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

GnomAD3 exomes AF: 0.223 AC: 40806 AN: 182837 Hom.: 3218 AF XY: 0.224 AC XY: 15097 AN XY: 67303

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 SAS exome AF: 0.256

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.: 32 AF XY: 0.240 AC XY: 87072 AN XY: 363124

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.230 AC: 25074 AN: 109220 Hom.: 2214 Cov.: 21 AF XY: 0.221 AC XY: 6963 AN XY: 31550

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.219

Alfa AF: 0.239 Hom.: 15993

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

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.31
DANN	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs1048118; hg19: chrX-47483800; COSMIC: COSV55950183; COSMIC: COSV55950183;