Variant 1-196651787-C-T 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 ENST00000359637.3(CFH):c.-331C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 327,434 control chromosomes in the GnomAD database, including 12,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5012 hom., cov: 32)

Exomes 𝑓: 0.28 ( 7884 hom. )

Consequence

CFH
ENST00000359637.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.312

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-196651787-C-T is Benign according to our data. Variant chr1-196651787-C-T is described in ClinVar as [Benign]. Clinvar id is 1249325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196651787-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000359637.3 linkuse as main transcript	c.-331C>T		5_prime_UTR_variant	1/9	1
CFH	ENST00000695968.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34633

AN:

151936

Hom.:

5008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.282

AC:

49479

AN:

175378

Hom.:

7884

AF XY:

0.283

AC XY:

26111

AN XY:

92422

show subpopulations

Gnomad4 AFR exome

AF:

0.0690

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.228

AC:

34627

AN:

152056

Hom.:

5012

Cov.:

AF XY:

0.226

AC XY:

16832

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0744

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.528

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.286

Hom.:

11407

Bravo

AF:

0.232

Asia WGS

AF:

0.308

AC:

1073

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	This variant is associated with the following publications: (PMID: 14583443, 21868097) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CFH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

DANN

Benign

0.76

Splicing

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