NM_000186.4:c.1520-98G>T

Variant names:

Variant summary

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

The NM_000186.4(CFH):c.1520-98G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 934,154 control chromosomes in the GnomAD database, including 188,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33427 hom., cov: 33)

Exomes 𝑓: 0.62 ( 155320 hom. )

Consequence

CFH
NM_000186.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.946

Publications

20 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:

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=-1.0).

BP6

Variant 1-196715495-G-T is Benign according to our data. Variant chr1-196715495-G-T is described in ClinVar as Benign. ClinVar VariationId is 1258057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFH	NM_000186.4 link	c.1520-98G>T		intron_variant	Intron 10 of 21	ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9 link	c.1520-98G>T		intron_variant	Intron 10 of 21	1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1 link	c.1520-98G>T		intron_variant	Intron 10 of 26			ENSP00000512341.1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99559

AN:

151886

Hom.:

33388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.947

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.675

GnomAD4 exome

AF:

0.623

AC:

487239

AN:

782150

Hom.:

155320

AF XY:

0.624

AC XY:

258014

AN XY:

413726

show subpopulations

African (AFR)

AF:

0.736

AC:

14654

AN:

19916

American (AMR)

AF:

0.816

AC:

32850

AN:

40266

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

13916

AN:

21102

East Asian (EAS)

AF:

0.939

AC:

33034

AN:

35178

South Asian (SAS)

AF:

0.687

AC:

47898

AN:

69708

European-Finnish (FIN)

AF:

0.539

AC:

23497

AN:

43626

Middle Eastern (MID)

AF:

0.632

AC:

2527

AN:

3996

European-Non Finnish (NFE)

AF:

0.578

AC:

295188

AN:

510646

Other (OTH)

AF:

0.628

AC:

23675

AN:

37712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8658

17316

25973

34631

43289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5016

10032

15048

20064

25080

<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:

0.656

AC:

99650

AN:

152004

Hom.:

33427

Cov.:

AF XY:

0.660

AC XY:

49022

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.736

AC:

30532

AN:

41500

American (AMR)

AF:

0.741

AC:

11293

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2319

AN:

3472

East Asian (EAS)

AF:

0.948

AC:

4911

AN:

5182

South Asian (SAS)

AF:

0.712

AC:

3436

AN:

4828

European-Finnish (FIN)

AF:

0.545

AC:

5746

AN:

10546

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.579

AC:

39327

AN:

67924

Other (OTH)

AF:

0.674

AC:

1425

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1735

3471

5206

6942

8677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.613

Hom.:

12882

Bravo

AF:

0.676

Asia WGS

AF:

0.787

AC:

2728

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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.1520-98G>T is an intronic variant located in intron 9. This variant is present at high allele frequency in population databases. In conclusion, we classify CFH c.1520-98G>T as a benign variant.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.49

(source)

DANN

Benign

0.47

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over