rs13117504

chr4-109737700-C-Gchr4-109737700-C-T

Variant summary

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

The NM_001375278.1(CFI):c.1559-2904G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,128 control chromosomes in the GnomAD database, including 11,774 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 0.37 (11774 hom., cov: 32)
• Consequence: CFI NM_001375278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFI	NM_001375278.1	c.1559-2904G>C		intron_variant
CFI	NM_001375279.1	c.1535-2904G>C		intron_variant
CFI	NM_001375280.1	c.1514-2904G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFI	ENST00000695844.1	n.1714-2904G>C		intron_variant, non_coding_transcript_variant
CFI	ENST00000695845.1	n.1712+4791G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56357 AN: 152010 Hom.: 11779 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56345 AN: 152128 Hom.: 11774 Cov.: 32 AF XY: 0.377 AC XY: 28071 AN XY: 74366

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.406

Alfa AF: 0.386 Hom.: 1508

Bravo AF: 0.365

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.8
Dann	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13117504; hg19: chr4-110658856;