NM_001145252.3:c.1244+212C>T

Variant names:

• chrX-47625846-G-A
• rs8177079
• NM_001145252.3:c.1244+212C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145252.3(CFP):​c.1244+212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.78 (23746 hom., 25077 hem., cov: 22)
  • Exomes 𝑓: 0.77 (68502 hom. 90453 hem.)
  • Failed GnomAD Quality Control
• Consequence: CFP NM_001145252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFP	NM_001145252.3	MANE Select	c.1244+212C>T		intron	N/A	NP_001138724.1	P27918
	CFP	NM_002621.2		c.1244+212C>T		intron	N/A	NP_002612.1	A0A0S2Z4I5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFP	ENST00000396992.8	TSL:1 MANE Select	c.1244+212C>T		intron	N/A	ENSP00000380189.3	P27918
	CFP	ENST00000247153.7	TSL:5	c.1244+212C>T		intron	N/A	ENSP00000247153.3	P27918
	CFP	ENST00000862734.1		c.1244+212C>T		intron	N/A	ENSP00000532793.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 85591 AN: 109934 Hom.: 23749 Cov.: 22

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.781

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.772 AC: 266343 AN: 345106 Hom.: 68502 Cov.: 3 AF XY: 0.770 AC XY: 90453 AN XY: 117542

African (AFR) AF: 0.824 AC: 8727 AN: 10586

American (AMR) AF: 0.752 AC: 15241 AN: 20275

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 9091 AN: 10867

East Asian (EAS) AF: 0.984 AC: 22649 AN: 23021

South Asian (SAS) AF: 0.735 AC: 22102 AN: 30079

European-Finnish (FIN) AF: 0.785 AC: 20033 AN: 25518

Middle Eastern (MID) AF: 0.754 AC: 1299 AN: 1723

European-Non Finnish (NFE) AF: 0.747 AC: 151471 AN: 202740

Other (OTH) AF: 0.775 AC: 15730 AN: 20297

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.779 AC: 85637 AN: 109989 Hom.: 23746 Cov.: 22 AF XY: 0.777 AC XY: 25077 AN XY: 32269

African (AFR) AF: 0.826 AC: 24852 AN: 30073

American (AMR) AF: 0.737 AC: 7657 AN: 10394

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2159 AN: 2628

East Asian (EAS) AF: 0.989 AC: 3468 AN: 3506

South Asian (SAS) AF: 0.751 AC: 1951 AN: 2599

European-Finnish (FIN) AF: 0.788 AC: 4573 AN: 5806

Middle Eastern (MID) AF: 0.803 AC: 171 AN: 213

European-Non Finnish (NFE) AF: 0.743 AC: 39069 AN: 52594

Other (OTH) AF: 0.781 AC: 1175 AN: 1505

Alfa AF: 0.758 Hom.: 63235

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-0.073
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: rs8177079; hg19: chrX-47485245;