X-47627087-C-A

Position:

• chrX-47627087-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CFP	NM_001145252.3	c.766+54G>T		intron_variant		ENST00000396992.8	NP_001138724.1
CFP	NM_002621.2	c.766+54G>T		intron_variant			NP_002612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8	c.766+54G>T		intron_variant		1	NM_001145252.3	ENSP00000380189	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 34063 AN: 112336 Hom.: 4207 Cov.: 24 AF XY: 0.291 AC XY: 10070 AN XY: 34558

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

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.252

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.271

Alfa AF: 0.271 Hom.: 3919

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

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

Publications

LitVar

Other links and lift over

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