rs909523

Variant names:

• chrX-47627087-C-A
• rs909523
• NM_001145252.3:c.766+54G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145252.3(CFP):​c.766+54G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,188,514 control chromosomes in the GnomAD database, including 27,724 homozygotes. There are 96,423 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (4213 hom., 10102 hem., cov: 24)
  • Exomes 𝑓: 0.25 (23511 hom. 86321 hem.)
• Consequence: CFP NM_001145252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 6 publications found

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

ENSG00000283743 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFP	NM_001145252.3	c.766+54G>T		intron_variant	Intron 5 of 8	ENST00000396992.8	NP_001138724.1
CFP	NM_002621.2	c.766+54G>T		intron_variant	Intron 6 of 9		NP_002612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8	c.766+54G>T		intron_variant	Intron 5 of 8	1	NM_001145252.3	ENSP00000380189.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 34063 AN: 112336 Hom.: 4207 Cov.: 24

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.249 AC: 267906 AN: 1076126 Hom.: 23511 Cov.: 29 AF XY: 0.249 AC XY: 86321 AN XY: 346060

African (AFR) AF: 0.477 AC: 12419 AN: 26024

American (AMR) AF: 0.246 AC: 8240 AN: 33513

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3373 AN: 19064

East Asian (EAS) AF: 0.0856 AC: 2543 AN: 29711

South Asian (SAS) AF: 0.264 AC: 13795 AN: 52327

European-Finnish (FIN) AF: 0.218 AC: 8590 AN: 39364

Middle Eastern (MID) AF: 0.246 AC: 1004 AN: 4082

European-Non Finnish (NFE) AF: 0.250 AC: 206512 AN: 826769

Other (OTH) AF: 0.252 AC: 11430 AN: 45272

GnomAD4 genome AF: 0.303 AC: 34102 AN: 112388 Hom.: 4213 Cov.: 24 AF XY: 0.292 AC XY: 10102 AN XY: 34620

African (AFR) AF: 0.472 AC: 14593 AN: 30885

American (AMR) AF: 0.263 AC: 2839 AN: 10813

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 510 AN: 2660

East Asian (EAS) AF: 0.0826 AC: 293 AN: 3548

South Asian (SAS) AF: 0.248 AC: 691 AN: 2789

European-Finnish (FIN) AF: 0.204 AC: 1267 AN: 6220

Middle Eastern (MID) AF: 0.219 AC: 47 AN: 215

European-Non Finnish (NFE) AF: 0.250 AC: 13279 AN: 53030

Other (OTH) AF: 0.271 AC: 421 AN: 1552

Alfa AF: 0.265 Hom.: 5951

Bravo AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.58
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs909523; hg19: chrX-47486486; COSMIC: COSV55951787; COSMIC: COSV55951787;