rs1683563

Variant names:

• chr19-861593-C-A
• rs1683563
• NM_001928.4:c.358-106C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-861593-C-A
• chr19-861593-C-G
• chr19-861593-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001928.4(CFD):​c.358-106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,377,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000034 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: CFD NM_001928.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 11 publications found

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]

CFD Gene-Disease associations (from GenCC):

• recurrent Neisseria infections due to factor D deficiency

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000145 (178/1231336) while in subpopulation NFE AF = 0.000185 (175/945770). AF 95% confidence interval is 0.000162. There are 0 homozygotes in GnomAdExome4. There are 91 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFD	NM_001928.4	MANE Select	c.358-106C>A		intron	N/A	NP_001919.2
	CFD	NM_001317335.2		c.379-106C>A		intron	N/A	NP_001304264.1	K7ERG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFD	ENST00000327726.11	TSL:1 MANE Select	c.358-106C>A		intron	N/A	ENSP00000332139.4	P00746
	CFD	ENST00000592860.3	TSL:1	c.379-106C>A		intron	N/A	ENSP00000468253.1	K7ERG9
	CFD	ENST00000866187.1		c.358-106C>A		intron	N/A	ENSP00000536246.1

Frequencies

GnomAD3 genomes AF: 0.0000342 AC: 5 AN: 146330 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000751

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000145 AC: 178 AN: 1231336 Hom.: 0 AF XY: 0.000149 AC XY: 91 AN XY: 610338

African (AFR) AF: 0.00 AC: 0 AN: 28672

American (AMR) AF: 0.00 AC: 0 AN: 34922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23246

East Asian (EAS) AF: 0.00 AC: 0 AN: 34798

South Asian (SAS) AF: 0.00 AC: 0 AN: 74050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3762

European-Non Finnish (NFE) AF: 0.000185 AC: 175 AN: 945770

Other (OTH) AF: 0.0000572 AC: 3 AN: 52440

GnomAD4 genome AF: 0.0000342 AC: 5 AN: 146330 Hom.: 0 Cov.: 20 AF XY: 0.0000422 AC XY: 3 AN XY: 71032

African (AFR) AF: 0.00 AC: 0 AN: 39248

American (AMR) AF: 0.00 AC: 0 AN: 14660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4908

South Asian (SAS) AF: 0.00 AC: 0 AN: 4462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000751 AC: 5 AN: 66604

Other (OTH) AF: 0.00 AC: 0 AN: 1980

Alfa AF: 0.00 Hom.: 1194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.6
DANN	Benign	0.95
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs1683563; hg19: chr19-861593;