19-862912-C-T

Position:

• chr19-862912-C-T

Variant summary

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

The NM_001928.4(CFD):​c.616-180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 150,240 control chromosomes in the GnomAD database, including 38,690 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 0.71 (38690 hom., cov: 27)
• Consequence: CFD NM_001928.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

CFD (HGNC:2771): (complement factor D) This gene encodes a member of the S1, or chymotrypsin, family of serine peptidases. This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation. This protein also functions as an adipokine, a cell signaling protein secreted by adipocytes, which regulates insulin secretion in mice. Mutations in this gene underlie complement factor D deficiency, which is associated with recurrent bacterial meningitis infections in human patients. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protease. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFD	NM_001928.4	c.616-180C>T		intron_variant		ENST00000327726.11	NP_001919.2
CFD	NM_001317335.2	c.637-180C>T		intron_variant			NP_001304264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFD	ENST00000327726.11	c.616-180C>T		intron_variant		1	NM_001928.4	ENSP00000332139	P2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 106745 AN: 150124 Hom.: 38639 Cov.: 27

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.711 AC: 106849 AN: 150240 Hom.: 38690 Cov.: 27 AF XY: 0.707 AC XY: 51857 AN XY: 73308

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.717

Alfa AF: 0.675 Hom.: 6193

Bravo AF: 0.712

Asia WGS AF: 0.607 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.84

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: rs3826945; hg19: chr19-862912;