rs7356506

chr4-109762298-G-Achr4-109762298-G-Cchr4-109762298-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000204.5(CFI):c.483-606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,238 control chromosomes in the GnomAD database, including 32,368 homozygotes. 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 0.64 (32296 hom., cov: 31)
  • Exomes 𝑓: 0.64 (72 hom.)
• Consequence: CFI NM_000204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789

Genes affected

CFI (HGNC:5394): (complement factor I) This gene encodes a serine proteinase that is essential for regulating the complement cascade. The encoded preproprotein is cleaved to produce both heavy and light chains, which are linked by disulfide bonds to form a heterodimeric glycoprotein. This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. Mutations in this gene have been associated with a predisposition to atypical hemolytic uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immune deposits and age-related macular degeneration are other conditions associated with mutations of this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFI	NM_000204.5	c.483-606C>T		intron_variant		ENST00000394634.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFI	ENST00000394634.7	c.483-606C>T		intron_variant		1	NM_000204.5	P2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96984 AN: 151806 Hom.: 32281 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.636 AC: 201 AN: 316 Hom.: 72 Cov.: 0 AF XY: 0.603 AC XY: 111 AN XY: 184

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.639 AC: 97037 AN: 151922 Hom.: 32296 Cov.: 31 AF XY: 0.639 AC XY: 47451 AN XY: 74260

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.650

Alfa AF: 0.727 Hom.: 25549

Bravo AF: 0.620

Asia WGS AF: 0.692 AC: 2409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.2
Dann	Benign	0.34

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: rs7356506; hg19: chr4-110683454;