rs388862

chr1-196828162-G-Cchr1-196828162-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002113.3(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 NM_002113.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0750

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CFHR1	NM_002113.3	c.523G>C	p.Glu175Gln	missense_variant	4/6	ENST00000320493.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.163 AC: 11828 AN: 72534 Hom.: 1919 Cov.: 12

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

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.: 30 AF XY: 0.132 AC XY: 58826 AN XY: 444486

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.: 12 AF XY: 0.160 AC XY: 5585 AN XY: 34944

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.8
Dann	Benign	0.55
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.067
Sift	Benign	0.35	T
Sift4G	Benign	0.29	T
Polyphen		0.12	B
Vest4		0.042
MPC		0.86
ClinPred		0.0040	T
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

Other links and lift over

dbSNP: rs388862; hg19: chr1-196797292; COSMIC: COSV57625798; COSMIC: COSV57625798;