Variant rs388862 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 ENST00000320493.10(CFHR1):c.523G>C(p.Glu175Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 959,468 control chromosomes in the GnomAD database, including 50,301 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 1934 hom., cov: 12)

Exomes 𝑓: 0.13 ( 48367 hom. )

Consequence

CFHR1
ENST00000320493.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0750

Variant links:

Genes affected

CFHR1 (HGNC:4888): (complement factor H related 1) This gene encodes a secreted protein belonging to the complement factor H protein family. It binds to Pseudomonas aeruginosa elongation factor Tuf together with plasminogen, which is proteolytically activated. It is proposed that Tuf acts as a virulence factor by acquiring host proteins to the pathogen surface, controlling complement, and facilitating tissue invasion. Mutations in this gene are associated with an increased risk of atypical hemolytic-uremic syndrome. [provided by RefSeq, Oct 2009]

CFHR1 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 (MetaRNN=0.018653035).

BP6

Variant 1-196828162-G-C is Benign according to our data. Variant chr1-196828162-G-C is described in ClinVar as [Benign]. Clinvar id is 1241507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196828162-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR1	NM_002113.3 linkuse as main transcript	c.523G>C	p.Glu175Gln	missense_variant	4/6	ENST00000320493.10	NP_002104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10 linkuse as main transcript	c.523G>C	p.Glu175Gln	missense_variant	4/6	1	NM_002113.3	ENSP00000314299	P1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

11828

AN:

72534

Hom.:

1919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.0651

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.170

GnomAD3 exomes

AF:

0.113

AC:

18709

AN:

165808

Hom.:

8981

AF XY:

0.112

AC XY:

10008

AN XY:

89700

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0566

Gnomad NFE exome

AF:

0.0804

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.129

AC:

114031

AN:

886852

Hom.:

48367

Cov.:

AF XY:

0.132

AC XY:

58826

AN XY:

444486

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.373

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.163

AC:

11862

AN:

72616

Hom.:

1934

Cov.:

AF XY:

0.160

AC XY:

5585

AN XY:

34944

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.431

Hom.:

1645

ExAC

AF:

0.215

AC:

23240

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.8

DANN

Benign

0.55

DEOGEN2

Benign

0.012

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.18

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

-1.1

REVEL

Benign

0.067

Sift

Benign

0.35

Sift4G

Benign

0.29

Polyphen

0.12

Vest4

0.042

MPC

0.86

ClinPred

0.0040

GERP RS

-3.7

Varity_R

0.11

gMVP

0.57

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