Genetic Variant CFHR1:p.Thr196Thr (chr1-196828227-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002113.3(CFHR1):c.588A>G(p.Thr196Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 937,300 control chromosomes in the GnomAD database, including 51,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4307 hom., cov: 14)

Exomes 𝑓: 0.14 ( 47109 hom. )

Consequence

CFHR1
NM_002113.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0760

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-196828227-A-G is Benign according to our data. Variant chr1-196828227-A-G is described in ClinVar as [Benign]. Clinvar id is 1283250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196828227-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.076 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR1	NM_002113.3 link	c.588A>G	p.Thr196Thr	synonymous_variant	Exon 4 of 6	ENST00000320493.10	NP_002104.2	Q03591

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10 link	c.588A>G	p.Thr196Thr	synonymous_variant	Exon 4 of 6	1	NM_002113.3	ENSP00000314299.5		Q03591

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

20455

AN:

83704

Hom.:

4282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.158

AC:

25983

AN:

164024

Hom.:

12096

AF XY:

0.158

AC XY:

14037

AN XY:

89114

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.166

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.137

AC:

116548

AN:

853482

Hom.:

47109

Cov.:

AF XY:

0.141

AC XY:

60287

AN XY:

428190

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.245

AC:

20513

AN:

83818

Hom.:

4307

Cov.:

AF XY:

0.242

AC XY:

9799

AN XY:

40532

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.423

Hom.:

2111

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.4

DANN

Benign

0.70

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