X-47624273-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001145252.3(CFP):c.*2A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,208,148 control chromosomes in the GnomAD database, including 3 homozygotes. There are 197 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., 88 hem., cov: 22)
  • Exomes 𝑓: 0.00037 (3 hom. 109 hem.)
• Consequence: CFP NM_001145252.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-47624273-T-A is Benign according to our data. Variant chrX-47624273-T-A is described in ClinVar as [Benign]. Clinvar id is 3043044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00286 (316/110641) while in subpopulation AFR AF= 0.0099 (301/30411). AF 95% confidence interval is 0.00898. There are 0 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 84 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFP	NM_001145252.3	c.*2A>T		3_prime_UTR_variant	9/9	ENST00000396992.8
CFP	NM_002621.2	c.*2A>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFP	ENST00000396992.8	c.*2A>T		3_prime_UTR_variant	9/9	1	NM_001145252.3	P1
CFP	ENST00000247153.7	c.*2A>T		3_prime_UTR_variant	10/10	5		P1
CFP	ENST00000478222.1	n.533A>T		non_coding_transcript_exon_variant	3/3	2
CFP	ENST00000640573.1	n.1650A>T		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 311 AN: 110586 Hom.: 0 Cov.: 22 AF XY: 0.00256 AC XY: 84 AN XY: 32806

Gnomad AFR AF: 0.00976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000867

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000379

Gnomad OTH AF: 0.00272

GnomAD3 exomes AF: 0.000877 AC: 161 AN: 183521 Hom.: 0 AF XY: 0.000589 AC XY: 40 AN XY: 67949

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000510

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000524

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000370 AC: 406 AN: 1097507 Hom.: 3 Cov.: 30 AF XY: 0.000300 AC XY: 109 AN XY: 362871

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.000625

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000475

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00286 AC: 316 AN: 110641 Hom.: 0 Cov.: 22 AF XY: 0.00268 AC XY: 88 AN XY: 32871

Gnomad4 AFR AF: 0.00990

Gnomad4 AMR AF: 0.000866

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000379

Gnomad4 OTH AF: 0.00268

Alfa AF: 0.00270 Hom.: 6

Bravo AF: 0.00348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CFP-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 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
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.87
Dann	Benign	0.74

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: rs138490907; hg19: chrX-47483672;