4-109801730-T-C

Position:

• chr4-109801730-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000204.5(CFI):​c.57+185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,054 control chromosomes in the GnomAD database, including 31,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (31923 hom., cov: 33)
• Consequence: CFI NM_000204.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.308

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-109801730-T-C is Benign according to our data. Variant chr4-109801730-T-C is described in ClinVar as [Benign]. Clinvar id is 1235745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFI	NM_000204.5	c.57+185A>G		intron_variant		ENST00000394634.7	NP_000195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFI	ENST00000394634.7	c.57+185A>G		intron_variant		1	NM_000204.5	ENSP00000378130	P2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97717 AN: 151936 Hom.: 31906 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.643 AC: 97773 AN: 152054 Hom.: 31923 Cov.: 33 AF XY: 0.644 AC XY: 47888 AN XY: 74342

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.639

Alfa AF: 0.694 Hom.: 20250

Bravo AF: 0.624

Asia WGS AF: 0.689 AC: 2392 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.72

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: rs7671905; hg19: chr4-110722886; COSMIC: COSV67100077;