19-860852-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001928.4(CFD):c.213-9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,563,062 control chromosomes in the GnomAD database, including 250,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20334 hom., cov: 29)

Exomes 𝑓: 0.57 ( 229763 hom. )

Consequence

CFD
NM_001928.4 intron

Scores

Splicing: ADA: 0.00001004

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.435

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-860852-G-C is Benign according to our data. Variant chr19-860852-G-C is described in ClinVar as [Benign]. Clinvar id is 402532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-860852-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFD	NM_001928.4 link	c.213-9G>C		intron_variant	Intron 2 of 4	ENST00000327726.11	NP_001919.2	P00746
CFD	NM_001317335.2 link	c.234-9G>C		intron_variant	Intron 2 of 4		NP_001304264.1	P00746K7ERG9A6XNE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFD	ENST00000327726.11 link	c.213-9G>C		intron_variant	Intron 2 of 4	1	NM_001928.4	ENSP00000332139.4		P00746

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77131

AN:

151406

Hom.:

20331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.496

GnomAD2 exomes

AF:

0.519

AC:

86417

AN:

166666

AF XY:

0.527

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.577

Gnomad EAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.566

AC:

798983

AN:

1411540

Hom.:

229763

Cov.:

AF XY:

0.566

AC XY:

395604

AN XY:

699450

show subpopulations

African (AFR)

AF:

0.387

AC:

12584

AN:

32522

American (AMR)

AF:

0.440

AC:

16961

AN:

38538

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

14733

AN:

25396

East Asian (EAS)

AF:

0.302

AC:

11218

AN:

37148

South Asian (SAS)

AF:

0.539

AC:

44134

AN:

81926

European-Finnish (FIN)

AF:

0.656

AC:

25404

AN:

38718

Middle Eastern (MID)

AF:

0.419

AC:

2293

AN:

5472

European-Non Finnish (NFE)

AF:

0.585

AC:

639308

AN:

1093076

Other (OTH)

AF:

0.551

AC:

32348

AN:

58744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

21431

42862

64293

85724

107155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.509

AC:

77156

AN:

151522

Hom.:

20334

Cov.:

AF XY:

0.510

AC XY:

37749

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.392

AC:

16178

AN:

41296

American (AMR)

AF:

0.477

AC:

7273

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

2068

AN:

3472

East Asian (EAS)

AF:

0.298

AC:

1520

AN:

5106

South Asian (SAS)

AF:

0.517

AC:

2487

AN:

4812

European-Finnish (FIN)

AF:

0.652

AC:

6868

AN:

10532

Middle Eastern (MID)

AF:

0.424

AC:

123

AN:

290

European-Non Finnish (NFE)

AF:

0.576

AC:

39037

AN:

67746

Other (OTH)

AF:

0.490

AC:

1029

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1845

3689

5534

7378

9223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.548

Hom.:

4696

Bravo

AF:

0.493

Asia WGS

AF:

0.437

AC:

1521

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.54

PhyloP100

-0.43

Mutation Taster

=24/76

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000010

dbscSNV1_RF

Benign

0.0020

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

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19-860852-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over