Variant rs551397 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000186.4(CFH):c.59-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,542,258 control chromosomes in the GnomAD database, including 67,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 15261 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52647 hom. )

Consequence

CFH
NM_000186.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.145

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 1-196672942-C-T is Benign according to our data. Variant chr1-196672942-C-T is described in ClinVar as [Benign]. Clinvar id is 1209735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4 linkuse as main transcript	c.59-36C>T		intron_variant		ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3 linkuse as main transcript	c.59-36C>T		intron_variant			NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9 linkuse as main transcript	c.59-36C>T		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60359

AN:

151790

Hom.:

15215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.313

AC:

74917

AN:

239220

Hom.:

13483

AF XY:

0.303

AC XY:

39325

AN XY:

129900

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.260

AC:

360929

AN:

1390350

Hom.:

52647

Cov.:

AF XY:

0.259

AC XY:

180272

AN XY:

695552

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.414

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.398

AC:

60471

AN:

151908

Hom.:

15261

Cov.:

AF XY:

0.399

AC XY:

29656

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.718

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.241

Hom.:

3782

Bravo

AF:

0.418

Asia WGS

AF:

0.433

AC:

1504

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Factor H deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Hemolytic uremic syndrome, atypical, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Age related macular degeneration 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Basal laminar drusen

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.84

DANN

Benign

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over