chr1-196673839-C-CTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000186.4(CFH):c.245-10_245-9dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,480,524 control chromosomes in the GnomAD database, including 29,687 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4702 hom., cov: 23)

Exomes 𝑓: 0.23 ( 24985 hom. )

Consequence

CFH
NM_000186.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.0950

Publications

4 publications found

Variant links:

Genes affected

CFH (HGNC:4883): (complement factor H) This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]

CFH Gene-Disease associations (from GenCC):

primary membranoproliferative glomerulonephritis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
atypical hemolytic-uremic syndrome
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
hemolytic uremic syndrome, atypical, susceptibility to, 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
complement factor H deficiency
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
basal laminar drusen
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Doyne honeycomb retinal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dense deposit disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CFH links:

ENSG00000289697 (HGNC:):

ENSG00000289697 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-196673839-C-CTT is Benign according to our data. Variant chr1-196673839-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1166414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000186.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFH	NM_000186.4	MANE Select	c.245-10_245-9dupTT		splice_region intron	N/A	NP_000177.2
	CFH	NM_001014975.3		c.245-10_245-9dupTT		splice_region intron	N/A	NP_001014975.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFH	ENST00000367429.9	TSL:1 MANE Select	c.245-10_245-9dupTT	splice_region intron	N/A	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1		c.245-10_245-9dupTT	splice_region intron	N/A	ENSP00000512341.1
CFH	ENST00000630130.2	TSL:1	c.245-10_245-9dupTT	splice_region intron	N/A	ENSP00000487250.1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36634

AN:

150994

Hom.:

4684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.226

AC:

300352

AN:

1329416

Hom.:

24985

Cov.:

AF XY:

0.228

AC XY:

152069

AN XY:

667864

show subpopulations

African (AFR)

AF:

0.173

AC:

5352

AN:

30896

American (AMR)

AF:

0.290

AC:

12620

AN:

43514

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6085

AN:

25018

East Asian (EAS)

AF:

0.429

AC:

16089

AN:

37504

South Asian (SAS)

AF:

0.285

AC:

23403

AN:

82242

European-Finnish (FIN)

AF:

0.270

AC:

14118

AN:

52378

Middle Eastern (MID)

AF:

0.156

AC:

860

AN:

5502

European-Non Finnish (NFE)

AF:

0.210

AC:

209186

AN:

996762

Other (OTH)

AF:

0.227

AC:

12639

AN:

55600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

10515

21030

31544

42059

52574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7372

14744

22116

29488

36860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.243

AC:

36700

AN:

151108

Hom.:

4702

Cov.:

AF XY:

0.249

AC XY:

18396

AN XY:

73738

show subpopulations

African (AFR)

AF:

0.188

AC:

7746

AN:

41214

American (AMR)

AF:

0.314

AC:

4768

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

921

AN:

3458

East Asian (EAS)

AF:

0.496

AC:

2539

AN:

5118

South Asian (SAS)

AF:

0.329

AC:

1571

AN:

4778

European-Finnish (FIN)

AF:

0.281

AC:

2902

AN:

10320

Middle Eastern (MID)

AF:

0.145

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.228

AC:

15428

AN:

67754

Other (OTH)

AF:

0.247

AC:

517

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1317

2635

3952

5270

6587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.142

Hom.:

241

Bravo

AF:

0.243

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Dec 29, 2019

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Factor H deficiency;C0730295:Basal laminar drusen;C1853147:Age related macular degeneration 4;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1

Benign:1

Apr 21, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Factor H deficiency

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hemolytic uremic syndrome, atypical, susceptibility to, 1

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Basal laminar drusen

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Atypical hemolytic-uremic syndrome

Benign:1

Dec 30, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Age related macular degeneration 4

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Factor H deficiency;C0730295:Basal laminar drusen;C1853147:Age related macular degeneration 4;C2931788:Atypical hemolytic-uremic syndrome

Benign:1

Oct 02, 2025

Genomenon, Inc, Genomenon, Inc

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

CFH c.245-17_245-9T[11] is a duplication variant located in intron 2. This variant is present at high allele frequency in population databases. In conclusion, we classify CFH c.245-17_245-9T[11] as a benign variant.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.095

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over